WorldWideScience

Sample records for quantifying microbubble dynamics

  1. Dynamics of micro-bubble sonication inside a phantom vessel

    KAUST Repository

    Qamar, Adnan

    2013-01-10

    A model for sonicated micro-bubble oscillations inside a phantom vessel is proposed. The model is not a variant of conventional Rayleigh-Plesset equation and is obtained from reduced Navier-Stokes equations. The model relates the micro-bubble oscillation dynamics with geometric and acoustic parameters in a consistent manner. It predicts micro-bubble oscillation dynamics as well as micro-bubble fragmentation when compared to the experimental data. For large micro-bubble radius to vessel diameter ratios, predictions are damped, suggesting breakdown of inherent modeling assumptions for these cases. Micro-bubble response with acoustic parameters is consistent with experiments and provides physical insight to the micro-bubble oscillation dynamics.

  2. Dynamic interactions between microbubbles in water.

    Science.gov (United States)

    Vakarelski, Ivan U; Manica, Rogerio; Tang, Xiaosong; O'Shea, Sean J; Stevens, Geoffrey W; Grieser, Franz; Dagastine, Raymond R; Chan, Derek Y C

    2010-06-22

    The interaction between moving bubbles, vapor voids in liquid, can arguably represent the simplest dynamical system in continuum mechanics as only a liquid and its vapor phase are involved. Surprisingly, and perhaps because of the ephemeral nature of bubbles, there has been no direct measurement of the time-dependent force between colliding bubbles which probes the effects of surface deformations and hydrodynamic flow on length scales down to nanometers. Using ultrasonically generated microbubbles (approximately 100 microm size) that have been accurately positioned in an atomic force microscope, we have made direct measurements of the force between two bubbles in water under controlled collision conditions that are similar to Brownian particles in solution. The experimental results together with detailed modeling reveal the nature of hydrodynamic boundary conditions at the air/water interface, the importance of the coupling of hydrodynamic flow, attractive van der Waals-Lifshitz forces, and bubble deformation in determining the conditions and mechanisms that lead to bubble coalescence. The observed behavior differs from intuitions gained from previous studies conducted using rigid particles. These direct force measurements reveal no specific ion effects at high ionic strengths or any special role of thermal fluctuations in film thickness in triggering the onset of bubble coalescence.

  3. MODELING MICROBUBBLE DYNAMICS IN BIOMEDICAL APPLICATIONS

    Institute of Scientific and Technical Information of China (English)

    CHAHINE Georges L.; HSIAO Chao-Tsung

    2012-01-01

    Controlling mierobubble 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 viscousinviseid 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.

  4. Dynamic interactions between microbubbles in water

    OpenAIRE

    Vakarelski, Ivan U.; Manica, Rogerio; Tang, Xiaosong; O’Shea, Sean J.; Stevens, Geoffrey W.; Grieser, Franz; Raymond R. Dagastine; Chan, Derek Y. C.

    2010-01-01

    The interaction between moving bubbles, vapor voids in liquid, can arguably represent the simplest dynamical system in continuum mechanics as only a liquid and its vapor phase are involved. Surprisingly, and perhaps because of the ephemeral nature of bubbles, there has been no direct measurement of the time-dependent force between colliding bubbles which probes the effects of surface deformations and hydrodynamic flow on length scales down to nanometers. Using ultrasonically generated microbu...

  5. A novel microfluidic chip for assessing dynamic adhesion behavior of cell-targeting microbubbles.

    Science.gov (United States)

    Yan, Fei; Li, Xiang; Jiang, Chunxiang; Jin, Qiaofeng; Zhang, Zidong; Shandas, Robin; Wu, Junru; Liu, Xin; Zheng, Hairong

    2014-01-01

    The primary aim of this study was to develop a microfluidic chip to study the dynamic adhesion behavior of cell-targeted microbubbles. The microfluidic device is composed of polydimethylsiloxane and is fabricated using the soft lithography technique. Each chamber of the microfluidic chip comprises eight U-shaped microsieves, by which various flow velocity distributions are generated. LyP-1-conjugated microbubbles were prepared by coating the surface of the phospholipid shell of microbubbles with LyP-1 peptides via biotin-avidin linkage. Under static conditions, the resulting targeted microbubbles are able to bind onto the surface of cells on incubation with breast cancer cells. Under dynamic fluid conditions, the cell targeting efficiency of the microbubbles was assessed at various flow velocity distributions in a chamber. Accumulation of targeted microbubbles was strongly influenced by flow velocity. Better retention of targeted microbubbles on cell surfaces was achieved at low mean flow velocities (<0.03 cm/s), in agreement with our computer simulation results. In conclusion, our results indicate that the microfluidic system is a useful platform for studying the microbubble-cell adhesive interaction. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

  6. Cavitation dynamics and directional microbubble ejection induced by intense femtosecond laser pulses in liquids.

    Science.gov (United States)

    Faccio, D; Tamošauskas, G; Rubino, E; Darginavičius, J; Papazoglou, D G; Tzortzakis, S; Couairon, A; Dubietis, A

    2012-09-01

    We study cavitation dynamics when focusing ring-shaped femtosecond laser beams in water. This focusing geometry reduces detrimental nonlinear beam distortions and enhances energy deposition within the medium, localized at the focal spot. We observe remarkable postcollapse dynamics of elongated cavitation bubbles with high-speed ejection of microbubbles out of the laser focal region. Bubbles are ejected along the laser axis in both directions (away and towards the laser). The initial shape of the cavitation bubble is also seen to either enhance or completely suppress jet formation during collapse. In the absence of jetting, microbubble ejection occurs orthogonal to the laser propagation axis.

  7. Dynamic manipulation of the subharmonic scattering of phospholipid-coated microbubbles

    NARCIS (Netherlands)

    T. Faez (Telli); G. Renaud (G.); M. Defontaine (Marielle); S. Calle (Samuel); N. de Jong (Nico)

    2011-01-01

    textabstractIn this paper, the influence of a dynamic variation in the ambient pressure on the subharmonic response of phospholipid-coated microbubbles was investigated. The ambient pressure in water was modulated by a 2.5 kHz acoustic wave with a peak amplitude of 15 kPa. We investigated the fundam

  8. Dynamic manipulation of the subharmonic scattering of phospholipid-coated microbubbles

    NARCIS (Netherlands)

    Faez, Telli; Renaud, Guillaume; Defontaine, Marielle; Calle, Samuel; Jong, de Nico

    2011-01-01

    In this paper, the influence of a dynamic variation in the ambient pressure on the subharmonic response of phospholipid-coated microbubbles was investigated. The ambient pressure in water was modulated by a 2.5 kHz acoustic wave with a peak amplitude of 15 kPa. We investigated the fundamental and su

  9. Experimental Method for Microbubbles Dynamics Monitoring and Radius Sizing

    Science.gov (United States)

    Fouan, Damien; Achaoui, Younes; Payan, Cedric; Mensah, Serge

    Rationale and aim: Within the context of divers' decompression illness prevention, ultrasonic detection and sizing of circulating microbubbles in blood is of great interest. In order to be representative of the divers gas tension level (supersaturation) and thus, to optimize decompression stages, the measurements (made in the right ventricle region) should be performed during a short period of time (ventricle filling <20 ms), efficient to detect a broad range of bubbles' radii population (radius from 20 to 200 _m) and harmless (Mechanical Index MI<0.3).

  10. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Cheng, Zhen; Davis, Corrine;

    2008-01-01

    To evaluate in vivo whole-body biodistribution of microbubbles (MBs) targeted to tumor angiogenesis-related vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by using dynamic micro-positron emission tomography (PET) in living mice....

  11. Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure.

    Science.gov (United States)

    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.

  12. Dynamic manipulation of the subharmonic scattering of phospholipid-coated microbubbles.

    Science.gov (United States)

    Faez, Telli; Renaud, Guillaume; Defontaine, Marielle; Calle, Samuel; de Jong, Nico

    2011-10-07

    In this paper, the influence of a dynamic variation in the ambient pressure on the subharmonic response of phospholipid-coated microbubbles was investigated. The ambient pressure in water was modulated by a 2.5 kHz acoustic wave with a peak amplitude of 15 kPa. We investigated the fundamental and subharmonic emissions at two driving frequencies: 5 and 10 MHz. The modulation of the bubble radius induced by the dynamic variation in the liquid ambient pressure subsequently causes modulations of the scattered acoustic pressure at the fundamental and subharmonic frequencies (half the fundamental frequency). As a first result, we measured that the variation in the ambient pressure of 15 kPa can modulate the subharmonic amplitude up to 10 dB as compared to the static atmospheric pressure condition. As a second result, we noticed that the relative subharmonic amplitude modulation as a function of the LF acoustic pressure was symmetrical for the 5 MHz driving frequency but asymmetric for 10 MHz. In the latter case, the subharmonic amplitude was more enhanced for an ambient overpressure than reduced for an ambient depression of the same amplitude likely due to the buckling of the lipid shell. However, the fundamental amplitude was symmetrically modulated during bubble compression and expansion. Moreover, subharmonic and fundamental amplitude modulations were found to be either in phase or out of phase with the low-frequency acoustic pressure. Numerical simulations showed that this behavior can be obtained depending on the bubbles' diameter. The highest subharmonic amplitude was measured when microbubbles were insonified at 10 MHz. This fact together with the asymmetry observed in the subharmonic modulation suggests that smaller bubbles with a buckling shell are excited at 10 MHz compared to 5 MHz. These results present new potentials for in vitro characterization of contrast agent microbubbles and possibly a new imaging modality.

  13. Dynamic manipulation of the subharmonic scattering of phospholipid-coated microbubbles

    Energy Technology Data Exchange (ETDEWEB)

    Faez, Telli; Renaud, Guillaume; De Jong, Nico [Biomedical Engineering Thoraxcenter, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam (Netherlands); Defontaine, Marielle; Calle, Samuel, E-mail: t.faez@erasmusmc.nl [INSERM U930-CNRS ERL3106, Universite Francois Rabelais, UFR Medecine, 10 bd Tonnelle, 37000 Tours (France)

    2011-10-07

    In this paper, the influence of a dynamic variation in the ambient pressure on the subharmonic response of phospholipid-coated microbubbles was investigated. The ambient pressure in water was modulated by a 2.5 kHz acoustic wave with a peak amplitude of 15 kPa. We investigated the fundamental and subharmonic emissions at two driving frequencies: 5 and 10 MHz. The modulation of the bubble radius induced by the dynamic variation in the liquid ambient pressure subsequently causes modulations of the scattered acoustic pressure at the fundamental and subharmonic frequencies (half the fundamental frequency). As a first result, we measured that the variation in the ambient pressure of 15 kPa can modulate the subharmonic amplitude up to 10 dB as compared to the static atmospheric pressure condition. As a second result, we noticed that the relative subharmonic amplitude modulation as a function of the LF acoustic pressure was symmetrical for the 5 MHz driving frequency but asymmetric for 10 MHz. In the latter case, the subharmonic amplitude was more enhanced for an ambient overpressure than reduced for an ambient depression of the same amplitude likely due to the buckling of the lipid shell. However, the fundamental amplitude was symmetrically modulated during bubble compression and expansion. Moreover, subharmonic and fundamental amplitude modulations were found to be either in phase or out of phase with the low-frequency acoustic pressure. Numerical simulations showed that this behavior can be obtained depending on the bubbles' diameter. The highest subharmonic amplitude was measured when microbubbles were insonified at 10 MHz. This fact together with the asymmetry observed in the subharmonic modulation suggests that smaller bubbles with a buckling shell are excited at 10 MHz compared to 5 MHz. These results present new potentials for in vitro characterization of contrast agent microbubbles and possibly a new imaging modality.

  14. Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

    Science.gov (United States)

    Calvisi, Michael

    2016-11-01

    Ultrasound contrast agents (UCAs) are shell encapsulated microbubbles developed originally for ultrasound imaging enhancement. UCAs are more recently being exploited for therapeutic applications, such as for drug delivery, gene therapy, and tissue ablation. Ultrasound transducer pulses can induce spherical (radial) UCA oscillations, translation, and nonspherical shape oscillations, the dynamics of which are highly coupled. If driven sufficiently strongly, the ultrasound can induce breakup of UCAs, which can facilitate drug or gene delivery but should be minimized for imaging purposes to increase residence time and maximize diagnostic effect. Therefore, an understanding of the interplay between the acoustic driving and nonspherical shape mode stability of UCAs is essential for both diagnostic and therapeutic applications. In this work, we use both analytical and numerical methods to analyze shape mode stability for cases of small and large nonspherical oscillations, respectively. To analyze shape mode stability in the limit of small nonspherical perturbations, we couple a radial model of a lipid-coated microbubble with a model for bubble translation and nonspherical shape oscillation. This hybrid model is used to predict shape mode stability for ultrasound driving frequencies and pressure amplitudes of clinical interest. In addition, calculations of the stability of individual shape modes, residence time, maximum radius, and translation are provided with respect to acoustic driving parameters and compared to an unshelled bubble. The effects of shell elasticity, shell viscosity, and initial radius on stability are investigated. Furthermore, the well-established boundary element method (BEM) is used to investigate the dynamics and shape stability of large amplitude nonspherical oscillations of an ultrasonically-forced, polymer-coated microbubble near a rigid boundary. Different instability modes are identified based on the degree of jetting and proximity to the

  15. Oscillatory dynamics of a charged microbubble under ultrasound

    Indian Academy of Sciences (India)

    Thotreithem Hongray; B Ashok; J Balakrishnan

    2015-04-01

    Nonlinear oscillations of a bubble carrying a constant charge and suspended in a fluid, undergoing periodic forcing due to incident ultrasound are studied. The system exhibits period-doubling route to chaos and the presence of charge has the effect of advancing these bifurcations. The minimum magnitude of the charge min above which the bubble’s radial oscillations can occur above a certain velocity 1 is found to be related by a simple power law to the driving frequency of the acoustic wave. We find the existence of a critical frequency $_{H}$ above which uncharged bubbles necessarily have to oscillate at velocities below $c_{1}$. We further find that this critical frequency crucially depends upon the amplitude $P_{s}$ of the driving acoustic pressure wave. The temperature of the gas within the bubble is calculated. A critical value tr of $P_{s}$ equal to the upper transient threshold pressure demarcates two distinct regions of dependence of the maximal radial bubble velocity max and maximal internal temperature max. Above this pressure, max and max decrease with increasing , while below tr, they increase with . The dynamical effects of the charge, the driving pressure and frequency of ultrasound on the bubble are discussed.

  16. Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions.

    Science.gov (United States)

    Halldorsdottir, Valgerdur G; Dave, Jaydev K; Leodore, Lauren M; Eisenbrey, John R; Park, Suhyun; Hall, Anne L; Thomenius, Kai; Forsberg, Flemming

    2011-07-01

    Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60 degree angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa peak-to-peak and frequencies of 2.5-6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9-14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r = 0.98, p scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5-4.5 MHz and acoustic pressures from 0-3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

  17. Oscillatory Dynamics and In Vivo Photoacoustic Imaging Performance of Plasmonic Nanoparticle-Coated Microbubbles.

    Science.gov (United States)

    Dixon, Adam J; Hu, Song; Klibanov, Alexander L; Hossack, John A

    2015-07-01

    Microbubbles bearing plasmonic nanoparticles on their surface provide contrast enhancement for both photoacoustic and ultrasound imaging. In this work, the responses of microbubbles with surface-bound gold nanorods-termed AuMBs-to nanosecond pulsed laser excitation are studied using high-speed microscopy, photoacoustic imaging, and numerical modeling. In response to laser fluences below 5 mJ cm(-2) , AuMBs produce weak photoacoustic emissions and exhibit negligible microbubble wall motion. However, in reponse to fluences above 5 mJ cm(-2) , AuMBs undergo dramatically increased thermal expansion and emit nonlinear photoacoustic waves of over 10-fold greater amplitude than would be expected from freely dispersed gold nanorods. Numerical modeling suggests that AuMB photoacoustic responses to low laser fluences result from conductive heat transfer from the surface-bound nanorods to the microbubble gas core, whereas at higher fluences, explosive boiling may occur at the nanorod surface, producing vapor nanobubbles that contribute to rapid AuMB expansion. The results of this study indicate that AuMBs are capable of producing acoustic emissions of significantly higher amplitude than those produced by conventional sources of photoacoustic contrast. In vivo imaging performance of AuMBs in a murine kidney model suggests that AuMBs may be an effective alternative to existing contrast agents for noninvasive photoacoustic and ultrasound imaging applications.

  18. On the dynamics of StemBells: Microbubble-conjugated stem cells for ultrasound-controlled delivery

    Science.gov (United States)

    Kokhuis, Tom J. A.; Naaijkens, Benno A.; Juffermans, Lynda J. M.; Kamp, Otto; van der Steen, Antonius F. W.; Versluis, Michel; de Jong, Nico

    2017-07-01

    The use of stem cells for regenerative tissue repair is promising but hampered by the low number of cells delivered to the site of injury. To increase the delivery, we propose a technique in which stem cells are linked to functionalized microbubbles, creating echogenic complex dubbed StemBells. StemBells are highly susceptible to acoustic radiation force which can be employed after injection to push the StemBells locally to the treatment site. To optimally benefit from the delivery technique, a thorough characterization of the dynamics of StemBells during ultrasound exposure is needed. Using high-speed optical imaging, we study the dynamics of StemBells as a function of the applied frequency from which resonance curves were constructed. A theoretical model, based on a modified Rayleigh-Plesset type equation, captured the experimental resonance characteristics and radial dynamics in detail.

  19. Quantifying the evolutionary dynamics of language.

    Science.gov (United States)

    Lieberman, Erez; Michel, Jean-Baptiste; Jackson, Joe; Tang, Tina; Nowak, Martin A

    2007-10-11

    Human language is based on grammatical rules. Cultural evolution allows these rules to change over time. Rules compete with each other: as new rules rise to prominence, old ones die away. To quantify the dynamics of language evolution, we studied the regularization of English verbs over the past 1,200 years. Although an elaborate system of productive conjugations existed in English's proto-Germanic ancestor, Modern English uses the dental suffix, '-ed', to signify past tense. Here we describe the emergence of this linguistic rule amidst the evolutionary decay of its exceptions, known to us as irregular verbs. We have generated a data set of verbs whose conjugations have been evolving for more than a millennium, tracking inflectional changes to 177 Old-English irregular verbs. Of these irregular verbs, 145 remained irregular in Middle English and 98 are still irregular today. We study how the rate of regularization depends on the frequency of word usage. The half-life of an irregular verb scales as the square root of its usage frequency: a verb that is 100 times less frequent regularizes 10 times as fast. Our study provides a quantitative analysis of the regularization process by which ancestral forms gradually yield to an emerging linguistic rule.

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

    OpenAIRE

    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 colla...

  1. Superharmonic microbubble Doppler effect in ultrasound therapy

    Science.gov (United States)

    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

  2. Spark discharge in conductive liquid with microbubbles

    Science.gov (United States)

    Vetchinin, S. P.; Vasilyak, L. M.; Pecherkin, V. Ya; Panov, V. A.; Son, E. E.

    2016-11-01

    Pulse electrical breakdown in 15% water solution of Isopropyl alcohol with air microbubbles from a pointed anode has been studied experimentally. It is shown, that the breakdown is always initiated from the bright region near the anode (anode “spot”). Detailed investigation into dynamic current-voltage characteristics and synchronized images reveals that it is thermal instability in the near anode region that causes spark channel initiation and development. The breakdown voltage, spark channel propagation speed and short-circuit current increase when the microbubbles are presented in the solution. The spark channel propagation speed is about 4-12 m/s and grows along with microbubbles concentration.

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

    Science.gov (United States)

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

    2014-12-01

    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.

  4. In Vivo Characterization of Ultrasound Contrast Agents: Microbubble Spectroscopy in a Chicken Embryo

    NARCIS (Netherlands)

    T. Faez (Telli); I. Skachkov (Ilya); M. Versluis (Michel); K. Kooiman (Klazina); N. de Jong (Nico)

    2012-01-01

    textabstractThe 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 i

  5. In Vivo Characterization of Ultrasound Contrast Agents: Microbubble Spectroscopy in a Chicken Embryo

    NARCIS (Netherlands)

    Faez, T.; Skachkov, I.; Versluis, M.; Kooiman, K.; Jong, de N.

    2012-01-01

    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,

  6. Quantifying the Dynamic Ocean Surface Using Underwater Radiometric Measurements

    Science.gov (United States)

    2015-03-31

    2. REPORT DATE 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 6. AUTHOR(S) 7. PERFORMING ORGANIZATION NAME(S) AND...WORK UNIT NUMBER 1. REPORT DATE (DD-MM-YYYY) 16. SECURITY CLASSIFICATION OF: PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 31-03-2015...Final March 2013 -- February 2015 Quantifying the Dynamic Ocean Surface Using Underwater Radiometric Measurements N00014-13-1-0352 Yue, Dick K.P

  7. Quantifying the Dynamic Ocean Surface Using Underwater Radiometric Measurement

    Science.gov (United States)

    2013-09-30

    Radiometric Measurement Lian Shen Department of Mechanical Engineering & St. Anthony Falls Laboratory University of Minnesota Minneapolis, MN...information if it does not display a currently valid OMB control number. 1. REPORT DATE 30 SEP 2013 2. REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00...2013 4. TITLE AND SUBTITLE Quantifying the Dynamic Ocean Surface Using Underwater Radiometric Measurement 5a. CONTRACT NUMBER 5b. GRANT NUMBER

  8. Mechanism and applications of the nonlinear dynamic resp onse to ultrasound contrast agent microbubbles%超声造影剂微泡非线性动力学响应的机理及相关应用∗

    Institute of Scientific and Technical Information of China (English)

    于洁; 郭霞生; 屠娟; 章东

    2015-01-01

    Ultrasound contrast agent (UCA) refers to the agent that has specific acoustic properties to enhance the contrast in ultrasound imaging by composition of gas-filled microbubbles with micrometer-diameters. In a diagnostic ultrasound field, microbubbles in fluid create an acoustic impedance mismatch between fluid and surrounding tissue to increase the reflection of sound and achieve a better contrast. Ongoing developments improve diagnostic possibilities of UCA remarkably, whereas their potential therapeutic applications have also been investigated for a couple of decades. The nonlinear response of UCA microbubbles has clinical relevance from both diagnostic and therapeutic perspectives. The aim of this review is to introduce the latest research progress of our group regarding the mechanism and applications of the nonlinear dynamic response to UCA, which include (1) an all-in-one solution characterizing coated bubble parameters with the help of the light scattering technique and flow cytometry, which makes it possible to quickly integrate the size distribution with dynamic motions of thousands of microbubbles and easily verify the validities of different shelled bubble dynamic models;(2) the development of a new bubble dynamics model that takes into account both nonlinear shell elasticity and viscosity, which can not only be capable of simulating the “compression-only” behavior of microbubbles excited by large amplitude ultrasound but also eliminate the dependence of bubble shell parameters on bubble size;(3) the estimation of UCA inertial cavitation thresholds of two types of commercial UCA microbubbles (viz. , SonoVue microbubbles coated with lipid shells and KangRun microbubbles coated with albumin shells) and the evaluation of the relationship between microbubble inertial cavitation thresholds and their shell parameters; and (4) the researches of DNA transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCA excited by 1-MHz

  9. Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)

    Science.gov (United States)

    Fritz, Andreas; Ptaszynski, Lars; Stoehr, Hardo; Brinkmann, Ralf

    2007-07-01

    Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.

  10. Quantifying dynamic characteristics of human walking for comprehensive gait cycle.

    Science.gov (United States)

    Mummolo, Carlotta; Mangialardi, Luigi; Kim, Joo H

    2013-09-01

    Normal human walking typically consists of phases during which the body is statically unbalanced while maintaining dynamic stability. Quantifying the dynamic characteristics of human walking can provide better understanding of gait principles. We introduce a novel quantitative index, the dynamic gait measure (DGM), for comprehensive gait cycle. The DGM quantifies the effects of inertia and the static balance instability in terms of zero-moment point and ground projection of center of mass and incorporates the time-varying foot support region (FSR) and the threshold between static and dynamic walking. Also, a framework of determining the DGM from experimental data is introduced, in which the gait cycle segmentation is further refined. A multisegmental foot model is integrated into a biped system to reconstruct the walking motion from experiments, which demonstrates the time-varying FSR for different subphases. The proof-of-concept results of the DGM from a gait experiment are demonstrated. The DGM results are analyzed along with other established features and indices of normal human walking. The DGM provides a measure of static balance instability of biped walking during each (sub)phase as well as the entire gait cycle. The DGM of normal human walking has the potential to provide some scientific insights in understanding biped walking principles, which can also be useful for their engineering and clinical applications.

  11. Quantifying chaotic dynamics from integrate-and-fire processes

    Energy Technology Data Exchange (ETDEWEB)

    Pavlov, A. N. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Saratov State Technical University, Politehnicheskaya Str. 77, 410054 Saratov (Russian Federation); Pavlova, O. N. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Mohammad, Y. K. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Tikrit University Salahudin, Tikrit Qadisiyah, University Str. P.O. Box 42, Tikrit (Iraq); Kurths, J. [Potsdam Institute for Climate Impact Research, Telegraphenberg A 31, 14473 Potsdam (Germany); Institute of Physics, Humboldt University Berlin, 12489 Berlin (Germany)

    2015-01-15

    Characterizing chaotic dynamics from integrate-and-fire (IF) interspike intervals (ISIs) is relatively easy performed at high firing rates. When the firing rate is low, a correct estimation of Lyapunov exponents (LEs) describing dynamical features of complex oscillations reflected in the IF ISI sequences becomes more complicated. In this work we discuss peculiarities and limitations of quantifying chaotic dynamics from IF point processes. We consider main factors leading to underestimated LEs and demonstrate a way of improving numerical determining of LEs from IF ISI sequences. We show that estimations of the two largest LEs can be performed using around 400 mean periods of chaotic oscillations in the regime of phase-coherent chaos. Application to real data is discussed.

  12. Detection of ultrasound contrast agent microbubble with constructed bubble wavelet

    Institute of Scientific and Technical Information of China (English)

    LI Bin; WAN Mingxi

    2005-01-01

    To detect the echo irradiated by microbubble out from the signal reflected by surrounding tissues, a mother wavelet named bubble wavelet according to the modified Herring oscillation equation was constructed and then applied to the original ultrasound radio frequency signal to perform the wavelet transformation. The transformed wavelet coefficients were extracted by selected threshold values to differentiate the echo of microbubble from signal of surround tissues. The effect of bubble wavelet was compared with other three commonly used mother wavelets by computer simulation and phantom experiment. The results demonstrated that there existed a highly correlation between the bubble wavelet and the experimental echo irradiated by microbubble because bubble wavelet had represented the dynamics of microbubble in advance. Furthermore, the wavelet transform results showed a better signal-noise-ratio and a sharper contrast between the echo of microbubble and the signal of surrounding tissues. Finally,constructing an overall mother wavelet library can improve the applicability and robustness of this detection method.

  13. Quantum process tomography quantifies coherence transfer dynamics in vibrational exciton.

    Science.gov (United States)

    Chuntonov, Lev; Ma, Jianqiang

    2013-10-31

    Quantum coherence has been a subject of great interest in many scientific disciplines. However, detailed characterization of the quantum coherence in molecular systems, especially its transfer and relaxation mechanisms, still remains a major challenge. The difficulties arise in part because the spectroscopic signatures of the coherence transfer are typically overwhelmed by other excitation-relaxation processes. We use quantum process tomography (QPT) via two-dimensional infrared spectroscopy to quantify the rate of the elusive coherence transfer between two vibrational exciton states. QPT retrieves the dynamics of the dissipative quantum system directly from the experimental observables. It thus serves as an experimental alternative to theoretical models of the system-bath interaction and can be used to validate these theories. Our results for coupled carbonyl groups of a diketone molecule in chloroform, used as a benchmark system, reveal the nonsecular nature of the interaction between the exciton and the Markovian bath and open the door for the systematic studies of the dissipative quantum systems dynamics in detail.

  14. The onset of microbubble vibration

    NARCIS (Netherlands)

    Emmer, M.; van Wamel, Annemieke; Goertz, David E.; de Jong, N.

    2007-01-01

    A linear relationship between the relative expansion of an off-resonance ultrasound contrast microbubble and low acoustic pressures is expected. In this study, high-speed optical recordings of individual phospholipid-coated microbubbles were used to investigate this relationship for microbubbles

  15. A Dynamic Method for Quantifying Natural Warming in Urban Areas

    Institute of Scientific and Technical Information of China (English)

    HE Yu-Ting; JIA Gen-Suo

    2012-01-01

    In the study of global warming, one of the main issues is the quantification of the urbanization effect in climate records. Previous studies have contributed much to removing the impact of urbanization from surface air temperature by carefully selecting reference sta- tions. However, due to the insufficient number of stations free from the influence of urbanization and the different criteria used to select reference stations, there are still significant controversies about the intensity of the impact of urbanization on temperature records. This study proposes a dynamic method for quantifying natural warming using information on urbanization from every station acquired from remote sensing (RS) data instead of selecting reference stations. Two different spatial scales were ap- plied to examine the impact of urbanization, but little difference was found, indicating the stability of this method. The results showed a significant difference in original temperature data and the homogenized data--urban warming accounted for approximately 64% in the original temperature warming but only approximately 20% in the homogenized temperature records.

  16. High-frequency capillary waves excited by oscillating microbubbles

    CERN Document Server

    Pommella, Angelo; Poulichet, Vincent; Garbin, Valeria

    2013-01-01

    This fluid dynamics video shows high-frequency capillary waves excited by the volumetric oscillations of microbubbles near a free surface. The frequency of the capillary waves is controlled by the oscillation frequency of the microbubbles, which are driven by an ultrasound field. Radial capillary waves produced by single bubbles and interference patterns generated by the superposition of capillary waves from multiple bubbles are shown.

  17. Microbubble clustering in turbulent flow

    CERN Document Server

    Calzavarini, E; Luther, S; Toschi, F; Van den Berg, T H; Berg, Thomas H. van den; Calzavarini, Enrico; Lohse, Detlef; Luther, Stefan; Toschi, Federico

    2006-01-01

    Single-point hot-wire measurements in the bulk of a turbulent channel have been performed in order to detect and quantify the phenomenon of preferential bubble accumulation. We show that statistical analysis of the bubble-probe colliding-times series can give a robust method for investigation of clustering in the bulk regions of a turbulent flow where, due to the opacity of the flow, no imaging technique can be employed. We demonstrate that micro-bubbles (radius R_0 ~ 0.1 mm) in a developed turbulent flow, where the Kolmogorov length-scale is, eta ~ R_0, display preferential concentration in small scale structures with a typical statistical signature ranging from the dissipative range, O(eta), up to the lower end of inertial range, O(100 eta). A comparison with Eulerian-Lagrangian numerical simulations is also performed and arising similarities and differences are discussed.

  18. Macroscopic acousto-mechanical analogy of a microbubble

    CERN Document Server

    Chaline, Jennifer; Mehrem, Ahmed; Bouakaz, Ayache; Santos, Serge Dos; Sánchez-Morcillo, Víctor J

    2015-01-01

    Microbubbles, either in the form of free gas bubbles surrounded by a fluid or encapsulated bubbles used currently as contrast agents for medical echography, exhibit complex dynamics under specific acoustic excitations. Nonetheless, considering their micron size and the complexity of their interaction phenomenon with ultrasound waves, expensive and complex experiments and/or simulations are required for their analysis. The behavior of a microbubble along its equator can be linked to a system of coupled oscillators. In this study, the oscillatory behavior of a microbubble has been investigated through an acousto-mechanical analogy based on a ring-shaped chain of coupled pendula. Observation of parametric vibration modes of the pendula ring excited at frequencies between $1$ and $5$ Hz is presented. Simulations have been carried out and show mode mixing phenomena. The relevance of the analogy between a microbubble and the macroscopic acousto-mechanical setup is discussed and suggested as an alternative way to in...

  19. Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection.

    Science.gov (United States)

    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.

  20. Quantifying the dynamics of coupled networks of switches and oscillators.

    Directory of Open Access Journals (Sweden)

    Matthew R Francis

    Full Text Available Complex network dynamics have been analyzed with models of systems of coupled switches or systems of coupled oscillators. However, many complex systems are composed of components with diverse dynamics whose interactions drive the system's evolution. We, therefore, introduce a new modeling framework that describes the dynamics of networks composed of both oscillators and switches. Both oscillator synchronization and switch stability are preserved in these heterogeneous, coupled networks. Furthermore, this model recapitulates the qualitative dynamics for the yeast cell cycle consistent with the hypothesized dynamics resulting from decomposition of the regulatory network into dynamic motifs. Introducing feedback into the cell-cycle network induces qualitative dynamics analogous to limitless replicative potential that is a hallmark of cancer. As a result, the proposed model of switch and oscillator coupling provides the ability to incorporate mechanisms that underlie the synchronized stimulus response ubiquitous in biochemical systems.

  1. Simulating Food Web Dynamics along a Gradient: Quantifying Human Influence

    OpenAIRE

    Ferenc Jordán; Nerta Gjata; Shu Mei; Yule, Catherine M.

    2012-01-01

    Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river...

  2. Microbubble Cavitation Imaging

    OpenAIRE

    Vignon, Francois; Shi, William T; Powers, Jeffry E.; Everbach, E. Carr; Liu, Jinjin; Gao, Shunji; Xie, Feng; Porter, Thomas R.

    2013-01-01

    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.

  3. Simulating food web dynamics along a gradient: quantifying human influence.

    Directory of Open Access Journals (Sweden)

    Ferenc Jordán

    Full Text Available Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo. The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1, when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling

  4. Simulating food web dynamics along a gradient: quantifying human influence.

    Science.gov (United States)

    Jordán, Ferenc; Gjata, Nerta; Mei, Shu; Yule, Catherine M

    2012-01-01

    Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics

  5. Microbubble cavitation imaging.

    Science.gov (United States)

    Vignon, Francois; Shi, William T; Powers, Jeffry E; Everbach, E Carr; Liu, Jinjin; Gao, Shunji; Xie, Feng; Porter, Thomas R

    2013-04-01

    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.

  6. Quantifying sudden changes in dynamical systems using symbolic networks

    CERN Document Server

    Masoller, Cristina; Ayad, Sarah; Gustave, Francois; Barland, Stephane; Pons, Antonio J; Gómez, Sergio; Arenas, Alex

    2015-01-01

    We characterise the evolution of a dynamical system by combining two well-known complex systems' tools, namely, symbolic ordinal analysis and networks. From the ordinal representation of a time-series we construct a network in which every node weights represents the probability of an ordinal patterns (OPs) to appear in the symbolic sequence and each edges weight represents the probability of transitions between two consecutive OPs. Several network-based diagnostics are then proposed to characterize the dynamics of different systems: logistic, tent and circle maps. We show that these diagnostics are able to capture changes produced in the dynamics as a control parameter is varied. We also apply our new measures to empirical data from semiconductor lasers and show that they are able to anticipate the polarization switchings, thus providing early warning signals of abrupt transitions.

  7. Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation

    Science.gov (United States)

    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

  8. Quantifying the Dynamical Complexity of Chaotic Time Series

    Science.gov (United States)

    Politi, Antonio

    2017-04-01

    A powerful approach is proposed for the characterization of chaotic signals. It is based on the combined use of two classes of indicators: (i) the probability of suitable symbolic sequences (obtained from the ordinal patterns of the corresponding time series); (ii) the width of the corresponding cylinder sets. This way, much information can be extracted and used to quantify the complexity of a given signal. As an example of the potentiality of the method, I introduce a modified permutation entropy which allows for quantitative estimates of the Kolmogorov-Sinai entropy in hyperchaotic models, where other methods would be unpractical. As a by-product, estimates of the fractal dimension of the underlying attractors are possible as well.

  9. Quantifying Chiral Magnetic Effect from Anomalous-Viscous Fluid Dynamics

    CERN Document Server

    Jiang, Yin; Yin, Yi; Liao, Jinfeng

    2016-01-01

    Chiral Magnetic Effect (CME) is the macroscopic manifestation of the fundamental chiral anomaly in a many-body system of chiral fermions, and emerges as anomalous transport current in the fluid dynamics framework. Experimental observation of CME is of great interest and has been reported in Dirac and Weyl semimetals. Significant efforts have also been made to search for CME in heavy ion collisions. Encouraging evidence of CME-induced charge separation in those collisions has been reported, albeit with ambiguity due to background contamination. Crucial for addressing such issue, is the need of quantitative predictions for CME signal with sophisticated modelings. In this paper we develop such a tool, the Anomalous Viscous Fluid Dynamics (AVFD) framework, which simulates the evolution of fermion currents in QGP on top of the data-validated VISHNU bulk hydrodynamic flow. With realistic initial conditions and magnetic field lifetime, the AVFD-predicted CME signal could be quantitatively consistent with measured ch...

  10. Schumpeterian economic dynamics as a quantifiable model of evolution

    Science.gov (United States)

    Thurner, Stefan; Klimek, Peter; Hanel, Rudolf

    2010-07-01

    We propose a simple quantitative model of Schumpeterian economic dynamics. New goods and services are endogenously produced through combinations of existing goods. As soon as new goods enter the market, they may compete against already existing goods. In other words, new products can have destructive effects on existing goods. As a result of this competition mechanism, existing goods may be driven out from the market—often causing cascades of secondary defects (Schumpeterian gales of destruction). The model leads to generic dynamics characterized by phases of relative economic stability followed by phases of massive restructuring of markets—which could be interpreted as Schumpeterian business 'cycles'. Model time series of product diversity and productivity reproduce several stylized facts of economics time series on long timescales, such as GDP or business failures, including non-Gaussian fat tailed distributions and volatility clustering. The model is phrased in an open, non-equilibrium setup which can be understood as a self-organized critical system. Its diversity dynamics can be understood by the time-varying topology of the active production networks.

  11. Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps

    Science.gov (United States)

    Nicholas, Jennifer; Christensen, Helen

    2016-01-01

    Background For many mental health conditions, mobile health apps offer the ability to deliver information, support, and intervention outside the clinical setting. However, there are difficulties with the use of a commercial app store to distribute health care resources, including turnover of apps, irrelevance of apps, and discordance with evidence-based practice. Objective The primary aim of this study was to quantify the longevity and rate of turnover of mental health apps within the official Android and iOS app stores. The secondary aim was to quantify the proportion of apps that were clinically relevant and assess whether the longevity of these apps differed from clinically nonrelevant apps. The tertiary aim was to establish the proportion of clinically relevant apps that included claims of clinical effectiveness. We performed additional subgroup analyses using additional data from the app stores, including search result ranking, user ratings, and number of downloads. Methods We searched iTunes (iOS) and the Google Play (Android) app stores each day over a 9-month period for apps related to depression, bipolar disorder, and suicide. We performed additional app-specific searches if an app no longer appeared within the main search Results On the Android platform, 50% of the search results changed after 130 days (depression), 195 days (bipolar disorder), and 115 days (suicide). Search results were more stable on the iOS platform, with 50% of the search results remaining at the end of the study period. Approximately 75% of Android and 90% of iOS apps were still available to download at the end of the study. We identified only 35.3% (347/982) of apps as being clinically relevant for depression, of which 9 (2.6%) claimed clinical effectiveness. Only 3 included a full citation to a published study. Conclusions The mental health app environment is volatile, with a clinically relevant app for depression becoming unavailable to download every 2.9 days. This poses

  12. Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps.

    Science.gov (United States)

    Larsen, Mark Erik; Nicholas, Jennifer; Christensen, Helen

    2016-08-09

    For many mental health conditions, mobile health apps offer the ability to deliver information, support, and intervention outside the clinical setting. However, there are difficulties with the use of a commercial app store to distribute health care resources, including turnover of apps, irrelevance of apps, and discordance with evidence-based practice. The primary aim of this study was to quantify the longevity and rate of turnover of mental health apps within the official Android and iOS app stores. The secondary aim was to quantify the proportion of apps that were clinically relevant and assess whether the longevity of these apps differed from clinically nonrelevant apps. The tertiary aim was to establish the proportion of clinically relevant apps that included claims of clinical effectiveness. We performed additional subgroup analyses using additional data from the app stores, including search result ranking, user ratings, and number of downloads. We searched iTunes (iOS) and the Google Play (Android) app stores each day over a 9-month period for apps related to depression, bipolar disorder, and suicide. We performed additional app-specific searches if an app no longer appeared within the main search On the Android platform, 50% of the search results changed after 130 days (depression), 195 days (bipolar disorder), and 115 days (suicide). Search results were more stable on the iOS platform, with 50% of the search results remaining at the end of the study period. Approximately 75% of Android and 90% of iOS apps were still available to download at the end of the study. We identified only 35.3% (347/982) of apps as being clinically relevant for depression, of which 9 (2.6%) claimed clinical effectiveness. Only 3 included a full citation to a published study. The mental health app environment is volatile, with a clinically relevant app for depression becoming unavailable to download every 2.9 days. This poses challenges for consumers and clinicians seeking relevant

  13. A method for differentiating targeted microbubbles in real time using subharmonic micro-ultrasound and interframe filtering.

    Science.gov (United States)

    Needles, A; Couture, O; Foster, F S

    2009-09-01

    This study introduces a new method for differentiating targeted microbubbles in the presence of flowing microbubbles and tissue using micro-ultrasound. The method relies on subharmonic (SH) imaging for segmenting microbubble signals from tissue signals, and low-pass interframe filtering for segmenting bound targeted microbubbles from flowing microbubbles. The method is evaluated with 30 frames per second SH B-mode imaging in vitro, using a wall-less vessel flow phantom. The SH B-mode cineloops were postprocessed using an interframe moving average filter to segment the regions of bound microbubbles on the inner surface of the vessel phantom. The bound bubbles were then disrupted with sufficiently high ultrasound pressures, so that the dynamic process of targeted microbubble binding under flowing conditions could be observed. These preliminary results show that the proposed method is a feasible solution to the challenge of differentiating targeted microbubbles in the presence of tissue and freely flowing microbubbles at high frequencies, which in turn should improve the specificity of targeted microbubble detection.

  14. Different approaches of symbolic dynamics to quantify heart rate complexity.

    Science.gov (United States)

    Cysarz, Dirk; Porta, Alberto; Montano, Nicola; Van Leeuwen, Peter; Kurths, Jürgen; Wessel, Niels

    2013-01-01

    The analysis of symbolic dynamics applied to physiological time series is able to retrieve information about dynamical properties of the underlying system that cannot be gained with standard methods like e.g. spectral analysis. Different approaches for the transformation of the original time series to the symbolic time series have been proposed. Yet the differences between the approaches are unknown. In this study three different transformation methods are investigated: (1) symbolization according to the deviation from the average time series, (2) symbolization according to several equidistant levels between the minimum and maximum of the time series, (3) binary symbolization of the first derivative of the time series. Each method was applied to the cardiac interbeat interval series RR(i) and its difference ΔRR(I) of 17 healthy subjects obtained during head-up tilt testing. The symbolic dynamics of each method is analyzed by means of the occurrence of short sequences ('words') of length 3. The occurrence of words is grouped according to words without variations of the symbols (0V%), words with one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%). Linear regression analysis showed that for method 1 0V%, 1V%, 2LV% and 2UV% changed with increasing tilt angle. For method 2 0V%, 2LV% and 2UV% changed with increasing tilt angle and method 3 showed changes for 0V% and 1V%. In conclusion, all methods are capable of reflecting changes of the cardiac autonomic nervous system during head-up tilt. All methods show that even the analysis of very short symbolic sequences is capable of tracking changes of the cardiac autonomic regulation during head-up tilt testing.

  15. Quantified Differential Dynamic Logic for Distributed Hybrid Systems

    Science.gov (United States)

    2010-05-01

    manual semantic reasoning. Other process- algebraic approaches, like χ [23], have been developed for modeling and sim- ulation. Verification is still...f(~s) using vectorial notation and we use ~s = ~t for element-wise equality. Formulas The formulas of QdL are defined as in first-order dynamic logic...like a Kleene algebra with tests [14]. QHPs are defined by the following grammar (α, β are QHPs, θ a term, i a variable of sort C, f is a function symbol

  16. 超声药物释放空化动力学行为研究%Investigation of Microbubble Dynamics in Drug Release by Ultrasound Cavitation

    Institute of Scientific and Technical Information of China (English)

    梁士利; 韩冬; 徐美玲; 崔霜; 张玲

    2012-01-01

    以直径1μm的脂质体为空化研究对象,从修正的Rayleigh空化方程入手,研究机械系数(MI)对300 kHz和1 MHz超声作用时空化效应的影响.脂质体的药物释放以超声作用前后脂质体中钙黄绿素的荧光强度为量度.模拟结果表明:在微泡振荡过程中,由超声波驱动产生的负向最大泡壁运动速度促使微泡半径从最大快速减小接近于零,微泡积聚到最大能量.对于300 kHz和1 MHz的激励超声,存在一个拐点(MI)值,当MI小于接近0.4时,1 MHz微泡半径变化幅度强于300 kHz;当MI>0.4时,300 kHz微泡半径变化幅度强于1MHz.这一结果预示在此范围内,300kHz的药物释放效果好于1MHz.本研究为超声空化效应研究及超声药物释放应用提供了理论依据.%The cavitation of a liposome microbubble dynamics in drug release was studied. The main objective of this work was to investigate the role by the mechanical index (MI) in the 300 kHz and 1MHz ultrasound. Several simulations indicated that bubble radius changes quickly from maximal value to zero by the driving frequency. Drug release was more efficient at 300 kHz compared to 1 MHz when MI was greater than 0.4. When the MI was less than 0.4, drug release was more efficient at 1 MHz compared to 300 kHz. The results demonstrate that ultrasound has a potential in enhancing drug release from liposome.

  17. NUMERICAL INVESTIGATIONS INTO THE FRICTION REDUCTION BY MICROBUBBLES FOR FLAT PLATES

    Institute of Scientific and Technical Information of China (English)

    Zhan De-xin; Wang Jia-mei; Lin Li-ming

    2003-01-01

    The two-dimensional flow on the flat plate with injected microbubbles is simulated using the software, PHOENICS (V3.2), usually used in the CFD (Computational Fluid Dynamics).A set of formulas for K-ε turbulence model modified with the presence of microbubbles, is employed.With considering the effect of gravity, interfacial lift, interphase friction, virtual mass force and interfacial pressure on the flow with microbubbles, numerical calculations for the influence of variable air volume fracton as well as distribution, injecting speed, microbubble diameter and position of introducing microbubbles on the friction reduction are presented.Results show that the friction reduction increases with increasing volume fraction and microbubble diameter within the range of 100μm, and that the velocity in the boundary layer with microbubbles is greater than that without microbubbles.The order of magnitude and trends of the experimental skin-friction are reproduced well.The uniform free-stream speed in all cases is 4m/s, giving Reynolds number of up to 20 million.

  18. Improved flow measurement using microbubble contrast agents and disruption-replenishment: clinical application to tumour monitoring.

    Science.gov (United States)

    Hudson, John M; Williams, Ross; Lloyd, Brendan; Atri, Mostafa; Kim, Tae Kyoung; Bjarnason, Georg; Burns, Peter N

    2011-08-01

    Dynamic contrast-enhanced ultrasound (DCE-US) and the method of disruption replenishment has been used for the past 10 years to measure flow noninvasively in the microcirculation. However, the method's perceived poor reproducibility remains a major impediment to widespread clinical acceptance. Poor reproducibility can be attributed, in part, to the curve fitting model that is used to quantify microbubble enhancement. Flow measurement in tumours is further complicated by the spatial and temporal heterogeneity of tumour blood flow. In this work, we evaluate three models of microbubble disruption and replenishment (mono-exponential, a simplified multivessel model by Krix and the lognormal perfusion model) using clinical data (11 patients, 41 sessions) from an antiangiogenic drug trial for metastatic renal cell carcinoma (RCC) and evaluate their contribution to the measurement's variability. Compared with the mono-exponential model, the lognormal perfusion model decreased the variability of intra-session velocity and blood volume measurements by 33% and 34%, respectively. Blood volume assessment using the lognormal perfusion model was comparable to Krix's mutlivessel model. Flow velocity measurement was 18% less variable for the lognormal perfusion model compared with the multivessel model. To further decrease flow measurement variability, we examine a method that exploits microbubble flow dynamics to discard the contribution of flow in large arteries and isolate the portion of the tumour microvasculature that is most sensitive to vessel targeting therapies. The method is validated with an in vitro phantom study prior to its application to the RCC clinical data set. Combined with the lognormal perfusion model, this method decreased the inter-plane variability of clinical measurements of relative tumour blood volume, in some cases by up to 20%.

  19. Quantifying Salmonella population dynamics in water and biofilms.

    Science.gov (United States)

    Sha, Qiong; Vattem, Dhiraj A; Forstner, Michael R J; Hahn, Dittmar

    2013-01-01

    Members of the bacterial genus Salmonella are recognized worldwide as major zoonotic pathogens often found to persist in non-enteric environments including heterogeneous aquatic biofilms. In this study, Salmonella isolates that had been detected repeatedly over time in aquatic biofilms at different sites in Spring Lake, San Marcos, Texas, were identified as serovars Give, Thompson, Newport and -:z10:z39. Pathogenicity results from feeding studies with the nematode Caenorhabditis elegans as host confirmed that these strains were pathogenic, with Salmonella-fed C. elegans dying faster (mean survival time between 3 and 4 days) than controls, i.e., Escherichia coli-fed C. elegans (mean survival time of 9.5 days). Cells of these isolates inoculated into water at a density of up to 10(6) ml(-1) water declined numerically by 3 orders of magnitude within 2 days, reaching the detection limit of our quantitative polymerase chain reaction (qPCR)-based quantification technique (i.e., 10(3) cells ml(-1)). Similar patterns were obtained for cells in heterogeneous aquatic biofilms developed on tiles and originally free of Salmonella that were kept in the inoculated water. Cell numbers increased during the first days to more than 10(7) cells cm(-2), and then declined over time. Ten-fold higher cell numbers of Salmonella inoculated into water or into biofilm resulted in similar patterns of population dynamics, though cells in biofilms remained detectable with numbers around 10(4) cells cm(-2) after 4 weeks. Independent of detectability by qPCR, samples of all treatments harbored viable salmonellae that resembled the inoculated isolates after 4 weeks of incubation. These results demonstrate that pathogenic salmonellae were isolated from heterogeneous aquatic biofilms and that they could persist and stay viable in such biofilms in high numbers for some time.

  20. Photothermal generation of microbubbles on plasmonic nanostructures inside microfluidic channels

    Science.gov (United States)

    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.

  1. The Design Of Microbubbles Specialized For Therapeutic Or Diagnostic Use

    Science.gov (United States)

    Kaneko, Yukio; Watanabe, Shunsuke; Yoshizawa, Shin; Takagi, Shu; Matsumoto, Yoichiro

    2005-03-01

    Medical applications which employ microbubbles, such as ultrasound imaging, gene transfer and sonodynamic therapy, are currently being investigated. In the field of bubble dynamics, it is known that bubbles can play a role in converting the mechanical energy of an ultrasound wave into not only energy of acoustic emission but also heat energy deposition when they are subjected to an oscillating field. In this study, the desired properties of the microbubble acting either as an echo source or a heat source are discussed. The type of gas inside a bubble has a strong effect on the energy radiation from the bubbles. It is shown that the balance between heat deposition and acoustic emission from the bubbles can be altered by changing the gas inside the bubbles. Consequently, HIFU treatment or ultrasound imaging can be carried out more effectively, utilizing these microbubbles.

  2. Quantifying the dynamic of OSA brain using multifractal formalism: A novel measure for sleep fragmentation.

    Science.gov (United States)

    Raiesdana, Somayeh

    2017-01-01

    It is thought that the critical brain dynamics in sleep is modulated during frequent periods of wakefulness. This paper utilizes the capacity of EEG based scaling analysis to quantify sleep fragmentation in patients with obstructive sleep apnea. The scale-free (fractal) behavior refers to a state where no characteristic scale dominates the dynamics of the underlying process which is evident as long range correlations in a time series. Here, Multiscaling (multifractal) spectrum is utilized to quantify the disturbed dynamic of an OSA brain with fragmented sleep. The whole night multichannel sleep EEG recordings of 18 subjects were employed to compute and quantify variable power-law long-range correlations and singularity spectra. Based on this characteristic, a new marker for sleep fragmentation named ``scaling based sleep fragmentation'' was introduced. This measure takes into account the sleep run length and stage transition quality within a fuzzy inference system to improve decisions made on sleep fragmentation. The proposed index was implemented, validated with sleepiness parameters and compared to some common indexes including sleep fragmentation index, arousal index, sleep diversity index, and sleep efficiency index. Correlations were almost significant suggesting that the sleep characterizing measure, based on singularity spectra range, could properly detect fragmentations and quantify their rate. This method can be an alternative for quantifying the sleep fragmentation in clinical practice after being approved experimentally. Control of sleep fragmentation and, subsequently, suppression of excessive daytime sleepiness will be a promising outlook of this kind of researches.

  3. Microvascular flow estimation by microbubble-assisted Nakagami imaging.

    Science.gov (United States)

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng

    2009-04-01

    The destruction and replenishment of microbubbles 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 the conventional B-mode images reflects the flow velocity. In this study, we monitored microbubble replenishment using a new proposed approach called the time-Nakagami-parameter curve (TNC) obtained from the parametric image based on the Nakagami statistical parameter for quantifying the microvascular flow velocity. The Nakagami parameter is estimated from signal envelope to reflect the backscattered statistics. The feasibility of using the TNC to estimate the microvascular flow was explored by carrying out phantom measurements and in vivo animal experiments. The rates of increase of the TIC and TNC were quantified as the rate constants beta(I) and beta(N) of monoexponential fitted curves, respectively. The experimental results showed that beta(N) behaves similarly to the conventional beta(I) in quantifying the flow velocity. Moreover, the tolerance to the effects of clutter is greater for the TNC than for the TIC, which makes it possible to use beta(N) to differentiate various flow velocities even when the ROI contains nonperfused areas. This finding suggests that the TNC-based technique can be used as a complementary tool for the conventional TIC to improve measurement of blood flow in the microcirculation.

  4. Acoustical Properties of Individual Liposome-Loaded Microbubbles

    NARCIS (Netherlands)

    Luan, Y.; Faez, T.; Gelderblom, E.C.; Skachkov, I.; Geers, B.; Lentacker, I.; Steen, van der T.; Versluis, M.; Jong, de N.

    2012-01-01

    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 loa

  5. Applications of Magnetic Microbubbles for Theranostics

    Directory of Open Access Journals (Sweden)

    Xiaowei Cai, Fang Yang, Ning Gu

    2012-01-01

    Full Text Available Compared with other diagnostic methods, ultrasound is proven to be a safe, simple, non-invasive and cost-effective imaging technique, but the resolution is not comparable to that of magnetic resonance imaging (MRI. Contrast-enhanced ultrasound employing microbubbles can gain a better resolution and is now widely used to diagnose a number of diseases in the clinic. For the last decade, microbubbles have been widely used as ultrasound contrast agents, drug delivery systems and nucleic acid transfection tools. However, microbubbles are not fairly stable enough in some conditions and are not well administrated distributed in the circulation system. On the other hand, magnetic nanoparticles, as MRI contrast agents, can non-specifically penetrate into normal tissues because of their relatively small sizes. By taking advantage of these two kinds of agents, the magnetic microbubbles which couple magnetic iron oxides nanoparticles in the microbubble structure have been explored. The stability of microbubbles can be raised by encapsulating magnetic nanoparticles into the bubble shells and with the guidance of magnetic field, magnetic microbubbles can be delivered to regions of interest, and after appropriate ultrasound exposure, the nanoparticles can be released to the desired area while the magnetic microbubbles collapse. In this review, we summarize magnetic microbubbles used in diagnostic and therapeutic fields, and predict the potential applications of magnetic microbubbles in the future.

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

    Science.gov (United States)

    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.

  7. Quantifying dynamic sensitivity of optimization algorithm parameters to improve hydrological model calibration

    Science.gov (United States)

    Qi, Wei; Zhang, Chi; Fu, Guangtao; Zhou, Huicheng

    2016-02-01

    It is widely recognized that optimization algorithm parameters have significant impacts on algorithm performance, but quantifying the influence is very complex and difficult due to high computational demands and dynamic nature of search parameters. The overall aim of this paper is to develop a global sensitivity analysis based framework to dynamically quantify the individual and interactive influence of algorithm parameters on algorithm performance. A variance decomposition sensitivity analysis method, Analysis of Variance (ANOVA), is used for sensitivity quantification, because it is capable of handling small samples and more computationally efficient compared with other approaches. The Shuffled Complex Evolution method developed at the University of Arizona algorithm (SCE-UA) is selected as an optimization algorithm for investigation, and two criteria, i.e., convergence speed and success rate, are used to measure the performance of SCE-UA. Results show the proposed framework can effectively reveal the dynamic sensitivity of algorithm parameters in the search processes, including individual influences of parameters and their interactive impacts. Interactions between algorithm parameters have significant impacts on SCE-UA performance, which has not been reported in previous research. The proposed framework provides a means to understand the dynamics of algorithm parameter influence, and highlights the significance of considering interactive parameter influence to improve algorithm performance in the search processes.

  8. Nanoparticle Delivery Enhancement With Acoustically Activated Microbubbles

    Science.gov (United States)

    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

  9. Quantifying the interplay between environmental and social effects on aggregated-fish dynamics

    CERN Document Server

    Capello, Manuela; Cotel, Pascal; Deneubourg, Jean-Louis; Dagorn, Laurent

    2011-01-01

    Demonstrating and quantifying the respective roles of social interactions and external stimuli governing fish dynamics is key to understanding fish spatial distribution. If seminal studies have contributed to our understanding of fish spatial organization in schools, little experimental information is available on fish in their natural environment, where aggregations often occur in the presence of spatial heterogeneities. Here, we applied novel modeling approaches coupled to accurate acoustic tracking for studying the dynamics of a group of gregarious fish in a heterogeneous environment. To this purpose, we acoustically tracked with submeter resolution the positions of twelve small pelagic fish (Selar crumenophthalmus) in the presence of an anchored floating object, constituting a point of attraction for several fish species. We constructed a field-based model for aggregated-fish dynamics, deriving effective interactions for both social and external stimuli from experiments. We tuned the model parameters that...

  10. TMS-evoked changes in brain-state dynamics quantified by using EEG data.

    Science.gov (United States)

    Mutanen, Tuomas; Nieminen, Jaakko O; Ilmoniemi, Risto J

    2013-01-01

    To improve our understanding of the combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) method in general, it is important to study how the dynamics of the TMS-modulated brain activity differs from the dynamics of spontaneous activity. In this paper, we introduce two quantitative measures based on EEG data, called mean state shift (MSS) and state variance (SV), for evaluating the TMS-evoked changes in the brain-state dynamics. MSS quantifies the immediate TMS-elicited change in the brain state, whereas SV shows whether the rate at which the brain state changes is modulated by TMS. We report a statistically significant increase for a period of 100-200 ms after the TMS pulse in both MSS and SV at the group level. This indicates that the TMS-modulated brain state differs from the spontaneous one. Moreover, the TMS-modulated activity is more vigorous than the natural activity.

  11. Quantifying the dynamics of emotional expressions in family therapy of patients with anorexia nervosa.

    Science.gov (United States)

    Pezard, Laurent; Doba, Karyn; Lesne, Annick; Nandrino, Jean-Louis

    2017-03-23

    Emotional interactions have been considered dynamical processes involved in the affective life of humans and their disturbances may induce mental disorders. Most studies of emotional interactions have focused on dyadic behaviors or self-reports of emotional states but neglected the dynamical processes involved in family therapy. The main objective of this study is to quantify the dynamics of emotional expressions and their changes using the family therapy of patients with anorexia nervosa as an example. Nonlinear methods characterize the variability of the dynamics at the level of the whole therapeutic system and reciprocal influence between the participants during family therapy. Results show that the variability of the dynamics is higher at the end of the therapy than at the beginning. The reciprocal influences between therapist and each member of the family and between mother and patient decrease with the course of family therapy. Our results support the development of new interpersonal strategies of emotion regulation during family therapy. The quantification of emotional dynamics can help understanding the emotional processes underlying psychopathology and evaluating quantitatively the changes achieved by the therapeutic intervention.

  12. Linking Ventilation Heterogeneity Quantified via Hyperpolarized 3He MRI to Dynamic Lung Mechanics and Airway Hyperresponsiveness.

    Science.gov (United States)

    Lui, Justin K; Parameswaran, Harikrishnan; Albert, Mitchell S; Lutchen, Kenneth R

    2015-01-01

    Advancements in hyperpolarized helium-3 MRI (HP 3He-MRI) have introduced the ability to render and quantify ventilation patterns throughout the anatomic regions of the lung. The goal of this study was to establish how ventilation heterogeneity relates to the dynamic changes in mechanical lung function and airway hyperresponsiveness in asthmatic subjects. In four healthy and nine mild-to-moderate asthmatic subjects, we measured dynamic lung resistance and lung elastance from 0.1 to 8 Hz via a broadband ventilation waveform technique. We quantified ventilation heterogeneity using a recently developed coefficient of variation method from HP 3He-MRI imaging. Dynamic lung mechanics and imaging were performed at baseline, post-challenge, and after a series of five deep inspirations. AHR was measured via the concentration of agonist that elicits a 20% decrease in the subject's forced expiratory volume in one second compared to baseline (PC20) dose. The ventilation coefficient of variation was correlated to low-frequency lung resistance (R = 0.647, P ventilation heterogeneity. Also, the degree of AHR appears to be dependent on the degree to which baseline airway constriction creates baseline ventilation heterogeneity. HP 3He-MRI imaging may be a powerful predictor of the degree of AHR and in tracking the efficacy of therapy.

  13. Beneath aggregate stability - quantifying thermodynamic properties that drive soil structure dynamics

    Science.gov (United States)

    Hallett, Paul; Ogden, Mike; Karim, Kamal; Schmidt, Sonja; Yoshida, Shuichiro

    2014-05-01

    Soil aggregates are a figment of your energy input and initial boundary conditions, so the basic thermodynamics that drive soil structure formation are needed to understand soil structure dynamics. Using approaches from engineering and materials science, it is possible quantify basic thermodynamic properties, but at present tests are generally limited to highly simplified, often remoulded, soil structures. Although this presents limitations, the understanding of underlying processes driving soil structure dynamics is poor, which could be argued is due to the enormity of the challenge of such an incredibly complex system. Other areas of soil science, particularly soil water physics, relied on simplified structures to develop theories that can now be applied to more complex pore structures. We argue that a similar approach needs to gain prominence in the study of soil aggregates. An overview will be provided of approaches adapted from other disciplines to quantify particle bonding, fracture resistance, rheology and capillary cohesion of soil that drive its aggregation and structure dynamics. All of the tests are limited as they require simplified soil structures, ranging from repacked soils to flat surfaces coated with mineral particles. A brief summary of the different approaches will demonstrate the benefits of collecting basic physical data relevant to soil structure dynamics, including examples where they are vital components of models. The soil treatments we have tested with these engineering and materials science approaches include field soils from a range of management practices with differing clay and organic matters contents, amendment and incubation of soils with a range of microorganisms and substrates in the laboratory, model clay-sand mixes and planar mineral surfaces with different topologies. In addition to advocating the wider adoption of these approaches, we will discuss limitations and hope to stimulate discussion on how approaches could be improved

  14. Three-dimensional phenomena in microbubble acoustic streaming

    CERN Document Server

    Marin, Alvaro; Rallabandi, Bhargav; Wang, Cheng; Hilgenfeldt, Sascha; Kähler, Christian J

    2015-01-01

    Ultrasound-driven oscillating micro-bubbles have been used as active actuators in microfluidic devices to perform manifold tasks such as mixing, sorting and manipulation of microparticles. A common configuration consists on 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 semi-cylindrical shape that generate significant streaming flow. Due to the geometry of the channels, such flows have been generally considered as quasi two-dimensional. Similar assumptions are often made in many other microfluidic systems based on \\emph{flat} micro-channels. However, in this paper 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 \\emph{streamsurface} wi...

  15. Potential of Microbubbles as Fat Replacer

    NARCIS (Netherlands)

    Rovers, T.A.M.; Sala, Guido; Linden, Van der Erik; Meinders, M.B.J.

    2016-01-01

    The potential of microbubbles as fat replacers and texture modifiers was assessed by comparison of the rheological and tribological properties of model food systems that contained (1) microbubbles, (2) emulsion droplets or (3) no added colloidal structures. We used (a) liquids with thickener, (b)

  16. Targeted renal therapies through microbubbles and ultrasound

    NARCIS (Netherlands)

    Deelman, Leo E.; Decleves, Anne-Emilie; Rychak, Joshua J.; Sharma, Kumar

    2010-01-01

    Microbubbles and ultrasound enhance the cellular uptake of drugs (including gene constructs) into the kidney. Microbubble induced modifications to the size selectivity of the filtration capacity of the kidney may enable drugs to enter previously inaccessible compartments of the kidney. So far, negat

  17. Microbubbles for Molecular Imaging and Drug Delivery

    NARCIS (Netherlands)

    I. Skachkov (Ilya)

    2016-01-01

    markdownabstractIn my thesis, microbubbles (MBs) for ultrasound (US) imaging, ultrasound molecular imaging, and drug delivery were studied. Microbubbles are gas-encapsulated lipid or polymer shell coated micro-particles, widely used as ultrasound contrast agents (UCA). MBs oscillate in response to t

  18. Stable and transient subharmonic emissions from isolated contrast agent microbubbles.

    Science.gov (United States)

    Biagi, Elena; Breschi, Luca; Vannacci, Enrico; Masotti, Leonardo

    2007-03-01

    Ultrasound contrast agents (UCAs) have been widely studied in recent years in order to improve and develop new, sophisticated imaging techniques for clinical applications. In order to improve the understanding of microbubble-ultrasound interactions, an acoustic dynamic characterization of UCA microbubble behavior was performed in this work using a high frame-rate acquiring and processing system. This equipment is connected to a commercial scanner that provides RF beam-formed data with a frame-rate of 30 Hz. Acquired RF sequences allows us to follow the dynamics of cavitation mechanisms in its temporal evolution during different insonifying conditions. The experimental setup allowed us to keep the bubbles free in a spatial region of the supporting medium, thus avoiding boundary effects that can alter the ultrasound field and the scattered echo from bubbles. The work focuses on the study of subharmonic emission from an isolated bubble of contrast agent. In particular, the acoustic pressure threshold for a subharmonic stable emission was evaluated for a subset of 50 microbubbles at 3.3 MHz and at 5 MHz of insonation frequencies. An unexpected second pressure threshold, which caused the stand still of the subharmonic emission, was detected at 3.3 MHz and 5 MHz excitation frequencies. A transient subharmonic emission, which is hypothesized as being related to the formation of new free gas bubbles, was detected during the ultrasound-induced destruction of microbubbles. An experimental procedure was devised in order to investigate these behaviors and several sequences of RF echo signals and the related spectra, acquired from an isolated bubble in different insonation conditions, are presented and discussed in this paper.

  19. Pressure control for reduced microbubble formation

    Science.gov (United States)

    Braggin, Jennifer

    2009-03-01

    Microbubbles in leading-edge photoresist materials create a challenge to the demanding yield requirements of today's shrinking circuit designs. When microbubbles are dispensed onto a wafer surface, they can act as an additional lens in the exposure path, ultimately distorting the pattern and affecting yield. Proper filter selection, filter priming, and dispense settings chosen during process startup are critical to reducing microbubbles, but certain chemistries can continue to cause problems even if the process has been optimized. This paper presents the results of applying a small amount of positive pressure on the chemistry before the dispense nozzle to reduce microbubbles in top anti-reflective coating (TARC). A two-stage technology dispense system was utilized to adjust the pressure on the chemistry in the dispense line while an in-line optical particle counter monitored the microbubbles generated during the dispense process.

  20. Quantifying terrestrial ecosystem carbon dynamics in the Jinsha watershed, Upper Yangtze, China from 1975 to 2000

    Science.gov (United States)

    Zhao, Shuqing

    2010-01-01

    Quantifying the spatial and temporal dynamics of carbon stocks in terrestrial ecosystems and carbon fluxes between the terrestrial biosphere and the atmosphere is critical to our understanding of regional patterns of carbon budgets. Here we use the General Ensemble biogeochemical Modeling System to simulate the terrestrial ecosystem carbon dynamics in the Jinsha watershed of China’s upper Yangtze basin from 1975 to 2000, based on unique combinations of spatial and temporal dynamics of major driving forces, such as climate, soil properties, nitrogen deposition, and land use and land cover changes. Our analysis demonstrates that the Jinsha watershed ecosystems acted as a carbon sink during the period of 1975–2000, with an average rate of 0.36 Mg/ha/yr, primarily resulting from regional climate variation and local land use and land cover change. Vegetation biomass accumulation accounted for 90.6% of the sink, while soil organic carbon loss before 1992 led to a lower net gain of carbon in the watershed, and after that soils became a small sink. Ecosystem carbon sink/source patterns showed a high degree of spatial heterogeneity. Carbon sinks were associated with forest areas without disturbances, whereas carbon sources were primarily caused by stand-replacing disturbances. It is critical to adequately represent the detailed fast-changing dynamics of land use activities in regional biogeochemical models to determine the spatial and temporal evolution of regional carbon sink/source patterns.

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

    Directory of Open Access Journals (Sweden)

    Yali Xu

    2016-01-01

    Full Text Available 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.

  2. The value of time-intensity curves obtained after microbubble contrast agent injection to discriminate responders from non-responders to anti-inflammatory medication among patients with Crohn's disease.

    Science.gov (United States)

    Quaia, Emilio; Cabibbo, Biagio; De Paoli, Luca; Toscano, William; Poillucci, Gabriele; Cova, Maria Assunta

    2013-06-01

    To assess the value of time-intensity curves obtained after sulphur hefluoride-filled microbubble contrast agent injection to discriminate responders from non-responders among patients with Crohn's disease (CD). Forty-three patients (29 male and 14 female; mean age ± SD, 48.5 ± 17.17 years) with initial diagnosis of active CD were recruited. In each patient, the therapeutic outcome was assessed after 12 weeks from the beginning of pharmacologic treatment. The terminal ileal loop was scanned after sulphur hexafluoride-filled microbubble injection, and the digital cine-clip registered during the first-pass dynamic enhancement was quantified in gray-scale levels. The percentage of maximal enhancement, time to peak enhancement, and area under the time-intensity curve in responders vs. non-responders were compared by Mann-Whitney U non-parametric test. Responders (n = 25 patients) vs. non-responders (n = 18) differed in the area under the time-intensity curve (621.58 ± 374.53 vs. 1,199.64 ± 386.39 P < 0.05), while they did not differ in percentage of maximal enhancement (41.26 ± 15.22 vs. 43.17 ± 4.41, P = 0.25) and time to peak enhancement (11.31 ± 3.06 vs. 10.12 ± 3.47, P = 0.15). The area under the time-intensity curve obtained after microbubble injection was the only parameter to discriminate responders from non-responders among patients with CD during pharmacologic treatment. • Dynamic ultrasound using microbubble contrast agents can help assess inflammatory bowel disease • Time-intensity curves can assess therapeutic outcome in Crohn's disease (CD) • The area under the time-intensity curve differentiates responders from non-responders during pharmacological treatment.

  3. Micro-bubbles seeding for flow characterization

    Science.gov (United States)

    Aumelas, V.; Lecoffre, Y.; Maj, G.; Franc, J.-P.

    2016-11-01

    Micro-bubbles injection has long been used in hydrodynamic facilities for the control of dissolved and free air. In some cavitation tunnels [9], very large quantities of microbubbles (billions per second) are injected for rapid degassing and, in smaller quantities (millions per second), for cavitation nuclei seeding. Micro-bubbles can also be used as tracers for optical measurements including visualization, LDV or PIV. For these applications, bubbles must be sufficiently small to faithfully follow the flow. Depending on the quality and spatial characteristics of the micro-bubbles seeding, several optical methods can be applied: simple visualization gives access to semi-quantitative information on the behaviour of flows; LASER velocimetry provides information on the mean velocity and other temporal local characteristics of the flow. This paper presents some new micro-bubbles seeding devices recently developed by YLEC Consultants. These devices have been designed to fulfill specific requirements related to integration into cavitation tunnels and permit optical velocimetry measurement techniques such as Particle Image Velocimetry (PIV). The LEGI cavitation tunnel is the first tunnel which has been equipped with these microbubbles seeding systems dedicated to optical velocimetry. This paper presents the final integration schemes selected for micro-bubbles seeding into LEGI tunnel and discuss about practical concerns related to the use of the injection system for optical velocimetry.

  4. An IVUS Transducer for Microbubble Therapies

    Science.gov (United States)

    Kilroy, Joseph P.; Patil, Abhay V.; Rychak, Joshua J.; Hossack, John A.

    2014-01-01

    There is interest in examining the potential of modified intravascular ultrasound (IVUS) catheters to facilitate dual diagnostic and therapeutic roles using ultrasound plus microbubbles for localized drug delivery to the vessel wall. The goal of this study was to design, prototype, and validate an IVUS transducer for microbubble-based drug delivery. A 1-D acoustic radiation force model and finite element analysis guided the design of a 1.5-MHz IVUS transducer. Using the IVUS transducer, biotinylated microbubbles were displaced in water and bovine whole blood to the streptavidin-coated wall of a flow phantom by a 1.5-MHz center frequency, peak negative pressure = 70 kPa pulse with varying pulse repetition frequency (PRF) while monitoring microbubble adhesion with ultrasound. A fit was applied to the RF data to extract a time constant (τ). As PRF was increased in water, the time constant decreased (τ = 32.6 s, 1 kHz vs. τ = 8.2 s, 6 kHz), whereas in bovine whole blood an adhesion–no adhesion transition was found for PRFs ≥ 8 kHz. Finally, a fluorophore was delivered to an ex vivo swine artery using microbubbles and the IVUS transducer, resulting in a 6.6-fold increase in fluorescence. These results indicate the importance of PRF (or duty factor) for IVUS acoustic radiation force microbubble displacement and the potential for IVUS and microbubbles to provide localized drug delivery. PMID:24569249

  5. Using GPS technology to quantify human mobility, dynamic contacts and infectious disease dynamics in a resource-poor urban environment.

    Directory of Open Access Journals (Sweden)

    Gonzalo M Vazquez-Prokopec

    Full Text Available Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS data-loggers to track the fine-scale (within city mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80% movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study

  6. Using GPS technology to quantify human mobility, dynamic contacts and infectious disease dynamics in a resource-poor urban environment.

    Science.gov (United States)

    Vazquez-Prokopec, Gonzalo M; Bisanzio, Donal; Stoddard, Steven T; Paz-Soldan, Valerie; Morrison, Amy C; Elder, John P; Ramirez-Paredes, Jhon; Halsey, Eric S; Kochel, Tadeusz J; Scott, Thomas W; Kitron, Uriel

    2013-01-01

    Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80%) movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for

  7. Biosurfactants for microbubble preparation and application.

    Science.gov (United States)

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

    2011-01-17

    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.

  8. Quantifying the Relationship between Dynamical Cores and Physical Parameterizations by Geostatistical Methods

    Science.gov (United States)

    Yorgun, M. S.; Rood, R. B.

    2010-12-01

    The behavior of atmospheric models is sensitive to the algorithms that are used to represent the equations of motion. Typically, comprehensive models are conceived in terms of the resolved fluid dynamics (i.e. the dynamical core) and subgrid, unresolved physics represented by parameterizations. Deterministic weather predictions are often validated with feature-by-feature comparison. Probabilistic weather forecasts and climate projects are evaluated with statistical methods. We seek to develop model evaluation strategies that identify like “objects” - coherent systems with an associated set of measurable parameters. This makes it possible to evaluate processes in models without needing to reproduce the time and location of, for example, a particular observed cloud system. Process- and object-based evaluation preserves information in the observations by avoiding the need for extensive spatial and temporal averaging. As a concrete example, we focus on analyzing how the choice of dynamical core impacts the representation of precipitation in the Pacific Northwest of the United States, Western Canada, and Alaska; this brings attention to the interaction of the resolved and the parameterized components of the model. Two dynamical cores are considered within the Community Atmosphere Model. These are the Spectral (Eulerian), which relies on global basis functions and the Finite Volume (FV), which uses only local information. We introduce the concept of "meteorological realism" that is, do local representations of large-scale phenomena, for example, fronts and orographic precipitation, look like the observations? A follow on question is, does the representation of these phenomena improve with resolution? Our approach to quantify meteorological realism starts with methods of geospatial statistics. Specifically, we employ variography, which is a geostatistical method which is used to measure the spatial continuity of a regionalized variable, and principle component

  9. Recent advances quantifying the large wood dynamics in river basins: New methods and remaining challenges

    Science.gov (United States)

    Ruiz-Villanueva, Virginia; Piégay, Hervé; Gurnell, Angela A.; Marston, Richard A.; Stoffel, Markus

    2016-09-01

    Large wood is an important physical component of woodland rivers and significantly influences river morphology. It is also a key component of stream ecosystems. However, large wood is also a source of risk for human activities as it may damage infrastructure, block river channels, and induce flooding. Therefore, the analysis and quantification of large wood and its mobility are crucial for understanding and managing wood in rivers. As the amount of large-wood-related studies by researchers, river managers, and stakeholders increases, documentation of commonly used and newly available techniques and their effectiveness has also become increasingly relevant as well. Important data and knowledge have been obtained from the application of very different approaches and have generated a significant body of valuable information representative of different environments. This review brings a comprehensive qualitative and quantitative summary of recent advances regarding the different processes involved in large wood dynamics in fluvial systems including wood budgeting and wood mechanics. First, some key definitions and concepts are introduced. Second, advances in quantifying large wood dynamics are reviewed; in particular, how measurements and modeling can be combined to integrate our understanding of how large wood moves through and is retained within river systems. Throughout, we present a quantitative and integrated meta-analysis compiled from different studies and geographical regions. Finally, we conclude by highlighting areas of particular research importance and their likely future trajectories, and we consider a particularly underresearched area so as to stress the future challenges for large wood research.

  10. Quantifying the size-resolved dynamics of indoor bioaerosol transport and control.

    Science.gov (United States)

    Kunkel, S A; Azimi, P; Zhao, H; Stark, B C; Stephens, B

    2017-09-01

    Understanding the bioaerosol dynamics of droplets and droplet nuclei emitted during respiratory activities is important for understanding how infectious diseases are transmitted and potentially controlled. To this end, we conducted experiments to quantify the size-resolved dynamics of indoor bioaerosol transport and control in an unoccupied apartment unit operating under four different HVAC particle filtration conditions. Two model organisms (Escherichia coli K12 and bacteriophage T4) were aerosolized under alternating low and high flow rates to roughly represent constant breathing and periodic coughing. Size-resolved aerosol sampling and settle plate swabbing were conducted in multiple locations. Samples were analyzed by DNA extraction and quantitative polymerase chain reaction (qPCR). DNA from both organisms was detected during all test conditions in all air samples up to 7 m away from the source, but decreased in magnitude with the distance from the source. A greater fraction of T4 DNA was recovered from the aerosol size fractions smaller than 1 μm than E. coli K12 at all air sampling locations. Higher efficiency HVAC filtration also reduced the amount of DNA recovered in air samples and on settle plates located 3-7 m from the source. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Quantifying effects of abiotic and biotic drivers on community dynamics with multivariate autoregressive (MAR) models.

    Science.gov (United States)

    Hampton, Stephanie E; Holmes, Elizabeth E; Scheef, Lindsay P; Scheuerell, Mark D; Katz, Stephen L; Pendleton, Daniel E; Ward, Eric J

    2013-12-01

    Long-term ecological data sets present opportunities for identifying drivers of community dynamics and quantifying their effects through time series analysis. Multivariate autoregressive (MAR) models are well known in many other disciplines, such as econometrics, but widespread adoption of MAR methods in ecology and natural resource management has been much slower despite some widely cited ecological examples. Here we review previous ecological applications of MAR models and highlight their ability to identify abiotic and biotic drivers of population dynamics, as well as community-level stability metrics, from long-term empirical observations. Thus far, MAR models have been used mainly with data from freshwater plankton communities; we examine the obstacles that may be hindering adoption in other systems and suggest practical modifications that will improve MAR models for broader application. Many of these modifications are already well known in other fields in which MAR models are common, although they are frequently described under different names. In an effort to make MAR models more accessible to ecologists, we include a worked example using recently developed R packages (MAR1 and MARSS), freely available and open-access software.

  12. Micro-bubble generated by laser irradiation on an individual carbon nanocoil

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yanming, E-mail: amandaming@mail.dlut.edu.cn [School of Physics and Optoelectronic Technology, DUT, Linggong Road, Dalian 116024 (China); Pan, Lujun, E-mail: lpan@dlut.edu.cn [School of Physics and Optoelectronic Technology, DUT, Linggong Road, Dalian 116024 (China); Liu, Yuli, E-mail: liuyuli2005@163.com [School of Physics and Optoelectronic Technology, DUT, Linggong Road, Dalian 116024 (China); Sun, Tao, E-mail: 332077309@qq.com [School of Energy and Power Engineering, DUT, Linggong Road, Dalian 116024 (China)

    2015-08-01

    Highlights: • We have investigated laser irradiated microbubbles which can be generated at fixed point on surface of an individual carbon nanocoil (CNC) immerged in deionized water. • The microbubble can be operated easily and flexibly. • Based on classical heat and mass transfer theories, the bubble growth data is in good agreement with the simplified model. - Abstract: We have investigated the micro-bubbles generated by laser induction on an individual carbon nanocoil (CNC) immerged in deionized water. The photon energy of the incident focused laser beam is absorbed by CNC and converted to thermal energy, which efficiently vaporizes the surrounding water, and subsequently a micro-bubble is generated at the laser location. The dynamics behavior of bubble generation, including its nucleation, expansion and steady-state, has been studied experimentally and theoretically. We have derived equations to analyze the expansion process of a bubble based on classical heat and mass transfer theories. The conclusion is in good agreement with the experiment. CNC, which acts as a realistic micro-bubble generator, can be operated easily and flexibly.

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

    Science.gov (United States)

    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.

  14. Ultrasound-induced encapsulated microbubble phenomena

    NARCIS (Netherlands)

    Postema, Michiel; Wamel, van Annemieke; Lancée, Charles T.; Jong, de Nico

    2004-01-01

    When encapsulated microbubbles are subjected to high-amplitude ultrasound, the following phenomena have been reported: oscillation, translation, coalescence, fragmentation, sonic cracking and jetting. In this paper, we explain these phenomena, based on theories that were validated for relatively big

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

    Science.gov (United States)

    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

  16. Quantifying the Relationship between Dynamical Cores and Physical Parameterizations by Object-Based Methods

    Science.gov (United States)

    Yorgun, M. S.; Rood, R. B.

    2011-12-01

    The behavior of atmospheric models is sensitive to the algorithms that are used to represent the equations of motion. Typically, comprehensive models are conceived in terms of the resolved fluid dynamics (i.e. the dynamical core) and subgrid, unresolved physics represented by parameterizations. Deterministic weather predictions are often validated with feature-by-feature comparison. Probabilistic weather forecasts and climate projects are evaluated with statistical methods. We seek to develop model evaluation strategies that identify like "objects" - coherent systems with an associated set of measurable parameters. This makes it possible to evaluate processes in models without needing to reproduce the time and location of, for example, a particular observed cloud system. Process- and object-based evaluation preserves information in the observations by avoiding the need for extensive spatial and temporal averaging. As a concrete example, we focus on analyzing how the choice of dynamical core impacts the representation of precipitation in the Pacific Northwest of the United States, Western Canada, and Alaska; this brings attention to the interaction of the resolved and the parameterized components of the model. Two dynamical cores are considered within the Community Atmosphere Model. These are the Spectral (Eulerian), which relies on global basis functions and the Finite Volume (FV), which uses only local information. We introduce the concept of "meteorological realism" that is, do local representations of large-scale phenomena, for example, fronts and orographic precipitation, look like the observations? A follow on question is, does the representation of these phenomena improve with resolution? Our approach to quantify meteorological realism starts with identification and isolation of key features of orographic precipitation that are represented differently by Spectral and FV models, using objective pattern recognition methods. Then we aim to quantitatively compare

  17. Biosurfactants for Microbubble Preparation and Application

    OpenAIRE

    Takeo Shiina; Zengshe Liu; Mitsutoshi Nakajima; Qingyi Xu

    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 im...

  18. Parallelized TCSPC for dynamic intravital fluorescence lifetime imaging: quantifying neuronal dysfunction in neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Jan Leo Rinnenthal

    Full Text Available Two-photon laser-scanning microscopy has revolutionized our view on vital processes by revealing motility and interaction patterns of various cell subsets in hardly accessible organs (e.g. brain in living animals. However, current technology is still insufficient to elucidate the mechanisms of organ dysfunction as a prerequisite for developing new therapeutic strategies, since it renders only sparse information about the molecular basis of cellular response within tissues in health and disease. In the context of imaging, Förster resonant energy transfer (FRET is one of the most adequate tools to probe molecular mechanisms of cell function. As a calibration-free technique, fluorescence lifetime imaging (FLIM is superior for quantifying FRET in vivo. Currently, its main limitation is the acquisition speed in the context of deep-tissue 3D and 4D imaging. Here we present a parallelized time-correlated single-photon counting point detector (p-TCSPC (i for dynamic single-beam scanning FLIM of large 3D areas on the range of hundreds of milliseconds relevant in the context of immune-induced pathologies as well as (ii for ultrafast 2D FLIM in the range of tens of milliseconds, a scale relevant for cell physiology. We demonstrate its power in dynamic deep-tissue intravital imaging, as compared to multi-beam scanning time-gated FLIM suitable for fast data acquisition and compared to highly sensitive single-channel TCSPC adequate to detect low fluorescence signals. Using p-TCSPC, 256×256 pixel FLIM maps (300×300 µm(2 are acquired within 468 ms while 131×131 pixel FLIM maps (75×75 µm(2 can be acquired every 82 ms in 115 µm depth in the spinal cord of CerTN L15 mice. The CerTN L15 mice express a FRET-based Ca-biosensor in certain neuronal subsets. Our new technology allows us to perform time-lapse 3D intravital FLIM (4D FLIM in the brain stem of CerTN L15 mice affected by experimental autoimmune encephalomyelitis and, thereby, to truly quantify

  19. Quantifying the effect of heat stress on daily milk yield and monitoring dynamic changes using an adaptive dynamic model.

    Science.gov (United States)

    André, G; Engel, B; Berentsen, P B M; Vellinga, Th V; Lansink, A G J M Oude

    2011-09-01

    Automation and use of robots are increasingly being used within dairy farming and result in large amounts of real time data. This information provides a base for the new management concept of precision livestock farming. From 2003 to 2006, time series of herd mean daily milk yield were collected on 6 experimental research farms in the Netherlands. These time series were analyzed with an adaptive dynamic model following a Bayesian method to quantify the effect of heat stress. The effect of heat stress was quantified in terms of critical temperature above which heat stress occurred, duration of heat stress periods, and resulting loss in milk yield. In addition, dynamic changes in level and trend were monitored, including the estimation of a weekly pattern. Monitoring comprised detection of potential outliers and other deteriorations. The adaptive dynamic model fitted the data well; the root mean squared error of the forecasts ranged from 0.55 to 0.99 kg of milk/d. The percentages of potential outliers and signals for deteriorations ranged from 5.5 to 9.7%. The Bayesian procedure for time series analysis and monitoring provided a useful tool for process control. Online estimates (based on past and present only) and retrospective estimates (determined afterward from all data) of level and trend in daily milk yield showed an almost yearly cycle that was in agreement with the calving pattern: most cows calved in winter and early spring versus summer and autumn. Estimated weekly patterns in terms of weekday effects could be related to specific management actions, such as change of pasture during grazing. For the effect of heat stress, the mean estimated critical temperature above which heat stress was expected was 17.8±0.56°C. The estimated duration of the heat stress periods was 5.5±1.03 d, and the estimated loss was 31.4±12.2 kg of milk/cow per year. Farm-specific estimates are helpful to identify management factors like grazing, housing and feeding, that affect the

  20. Quantifying Key Climate Parameter Uncertainties Using an Earth System Model with a Dynamic 3D Ocean

    Science.gov (United States)

    Olson, R.; Sriver, R. L.; Goes, M. P.; Urban, N.; Matthews, D.; Haran, M.; Keller, K.

    2011-12-01

    Climate projections hinge critically on uncertain climate model parameters such as climate sensitivity, vertical ocean diffusivity and anthropogenic sulfate aerosol forcings. Climate sensitivity is defined as the equilibrium global mean temperature response to a doubling of atmospheric CO2 concentrations. Vertical ocean diffusivity parameterizes sub-grid scale ocean vertical mixing processes. These parameters are typically estimated using Intermediate Complexity Earth System Models (EMICs) that lack a full 3D representation of the oceans, thereby neglecting the effects of mixing on ocean dynamics and meridional overturning. We improve on these studies by employing an EMIC with a dynamic 3D ocean model to estimate these parameters. We carry out historical climate simulations with the University of Victoria Earth System Climate Model (UVic ESCM) varying parameters that affect climate sensitivity, vertical ocean mixing, and effects of anthropogenic sulfate aerosols. We use a Bayesian approach whereby the likelihood of each parameter combination depends on how well the model simulates surface air temperature and upper ocean heat content. We use a Gaussian process emulator to interpolate the model output to an arbitrary parameter setting. We use Markov Chain Monte Carlo method to estimate the posterior probability distribution function (pdf) of these parameters. We explore the sensitivity of the results to prior assumptions about the parameters. In addition, we estimate the relative skill of different observations to constrain the parameters. We quantify the uncertainty in parameter estimates stemming from climate variability, model and observational errors. We explore the sensitivity of key decision-relevant climate projections to these parameters. We find that climate sensitivity and vertical ocean diffusivity estimates are consistent with previously published results. The climate sensitivity pdf is strongly affected by the prior assumptions, and by the scaling

  1. Utilizing dynamic tensiometry to quantify contact angle hysteresis and wetting state transitions on nonwetting surfaces.

    Science.gov (United States)

    Kleingartner, Justin A; Srinivasan, Siddarth; Mabry, Joseph M; Cohen, Robert E; McKinley, Gareth H

    2013-11-05

    Goniometric techniques traditionally quantify two parameters, the advancing and receding contact angles, that are useful for characterizing the wetting properties of a solid surface; however, dynamic tensiometry, which measures changes in the net force on a surface during the repeated immersion and emersion of a solid into a probe liquid, can provide further insight into the wetting properties of a surface. We detail a framework for analyzing tensiometric results that allows for the determination of wetting hysteresis, wetting state transitions, and characteristic topographical length scales on textured, nonwetting surfaces, in addition to the more traditional measurement of apparent advancing and receding contact angles. Fluorodecyl POSS, a low-surface-energy material, was blended with commercially available poly(methyl methacrylate) (PMMA) and then dip- or spray-coated onto glass substrates. These surfaces were probed with a variety of liquids to illustrate the effects of probe liquid surface tension, solid surface chemistry, and surface texture on the apparent contact angles and wetting hysteresis of nonwetting surfaces. Woven meshes were then used as model structured substrates to add a second, larger length scale for the surface texture. When immersed into a probe liquid, these spray-coated mesh surfaces can form a metastable, solid-liquid-air interface on the largest length scale of surface texture. The increasing hydrostatic pressure associated with progressively greater immersion depths disrupts this metastable, composite interface and forces penetration of the probe liquid into the mesh structure. This transition is marked by a sudden change in the wetting hysteresis, which can be systematically probed using spray-coated, woven meshes of varying wire radius and spacing. We also show that dynamic tensiometry can accurately and quantitatively characterize topographical length scales that are present on microtextured surfaces.

  2. Land cover change and remote sensing: Examples of quantifying spatiotemporal dynamics in tropical forests

    Energy Technology Data Exchange (ETDEWEB)

    Krummel, J.R.; Su, Haiping [Argonne National Lab., IL (United States); Fox, J. [East-West Center, Honolulu, HI (United States); Yarnasan, S.; Ekasingh, M. [Chiang Mai Univ. (Thailand)

    1995-06-01

    Research on human impacts or natural processes that operate over broad geographic areas must explicitly address issues of scale and spatial heterogeneity. While the tropical forests of Southeast Asia and Mexico have been occupied and used to meet human needs for thousands of years, traditional forest management systems are currently being transformed by rapid and far-reaching demographic, political, economic, and environmental changes. The dynamics of population growth, migration into the remaining frontiers, and responses to national and international market forces result in a demand for land to produce food and fiber. These results illustrate some of the mechanisms that drive current land use changes, especially in the tropical forest frontiers. By linking the outcome of individual land use decisions and measures of landscape fragmentation and change, the aggregated results shows the hierarchy of temporal and spatial events that in summation result in global changes to the most complex and sensitive biome -- tropical forests. By quantifying the spatial and temporal patterns of tropical forest change, researchers can assist policy makers by showing how landscape systems in these tropical forests are controlled by physical, biological, social, and economic parameters.

  3. Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

    Science.gov (United States)

    Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

    2016-04-01

    Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

  4. Market dynamics immediately before and after financial shocks: Quantifying the Omori, productivity, and Bath laws.

    Science.gov (United States)

    Petersen, Alexander M; Wang, Fengzhong; Havlin, Shlomo; Stanley, H Eugene

    2010-09-01

    We study the cascading dynamics immediately before and immediately after 219 market shocks. We define the time of a market shock T{c} to be the time for which the market volatility V(T{c}) has a peak that exceeds a predetermined threshold. The cascade of high volatility "aftershocks" triggered by the "main shock" is quantitatively similar to earthquakes and solar flares, which have been described by three empirical laws-the Omori law, the productivity law, and the Bath law. We analyze the most traded 531 stocks in U.S. markets during the 2 yr period of 2001-2002 at the 1 min time resolution. We find quantitative relations between the main shock magnitude M≡log{10} V(T{c}) and the parameters quantifying the decay of volatility aftershocks as well as the volatility preshocks. We also find that stocks with larger trading activity react more strongly and more quickly to market shocks than stocks with smaller trading activity. Our findings characterize the typical volatility response conditional on M , both at the market and the individual stock scale. We argue that there is potential utility in these three statistical quantitative relations with applications in option pricing and volatility trading.

  5. Market dynamics immediately before and after financial shocks: Quantifying the Omori, productivity, and Bath laws

    Science.gov (United States)

    Petersen, Alexander M.; Wang, Fengzhong; Havlin, Shlomo; Stanley, H. Eugene

    2010-09-01

    We study the cascading dynamics immediately before and immediately after 219 market shocks. We define the time of a market shock Tc to be the time for which the market volatility V(Tc) has a peak that exceeds a predetermined threshold. The cascade of high volatility “aftershocks” triggered by the “main shock” is quantitatively similar to earthquakes and solar flares, which have been described by three empirical laws—the Omori law, the productivity law, and the Bath law. We analyze the most traded 531 stocks in U.S. markets during the 2 yr period of 2001-2002 at the 1 min time resolution. We find quantitative relations between the main shock magnitude M≡log10V(Tc) and the parameters quantifying the decay of volatility aftershocks as well as the volatility preshocks. We also find that stocks with larger trading activity react more strongly and more quickly to market shocks than stocks with smaller trading activity. Our findings characterize the typical volatility response conditional on M , both at the market and the individual stock scale. We argue that there is potential utility in these three statistical quantitative relations with applications in option pricing and volatility trading.

  6. Quantifying microstructural dynamics and electrochemical activity of graphite and silicon-graphite lithium ion battery anodes

    Science.gov (United States)

    Pietsch, Patrick; Westhoff, Daniel; Feinauer, Julian; Eller, Jens; Marone, Federica; Stampanoni, Marco; Schmidt, Volker; Wood, Vanessa

    2016-01-01

    Despite numerous studies presenting advances in tomographic imaging and analysis of lithium ion batteries, graphite-based anodes have received little attention. Weak X-ray attenuation of graphite and, as a result, poor contrast between graphite and the other carbon-based components in an electrode pore space renders data analysis challenging. Here we demonstrate operando tomography of weakly attenuating electrodes during electrochemical (de)lithiation. We use propagation-based phase contrast tomography to facilitate the differentiation between weakly attenuating materials and apply digital volume correlation to capture the dynamics of the electrodes during operation. After validating that we can quantify the local electrochemical activity and microstructural changes throughout graphite electrodes, we apply our technique to graphite-silicon composite electrodes. We show that microstructural changes that occur during (de)lithiation of a pure graphite electrode are of the same order of magnitude as spatial inhomogeneities within it, while strain in composite electrodes is locally pronounced and introduces significant microstructural changes. PMID:27671269

  7. Single Microbubble Measurements of Lipid Monolayer Viscoelastic Properties for Small-Amplitude Oscillations.

    Science.gov (United States)

    Lum, Jordan S; Dove, Jacob D; Murray, Todd W; Borden, Mark A

    2016-09-20

    Lipid monolayer rheology plays an important role in a variety of interfacial phenomena, the physics of biological membranes, and the dynamic response of acoustic bubbles and drops. We show here measurements of lipid monolayer elasticity and viscosity for very small strains at megahertz frequency. Individual plasmonic microbubbles of 2-6 μm radius were photothermally activated with a short laser pulse, and the subsequent nanometer-scale radial oscillations during ring-down were monitored by optical scatter. This method provided average dynamic response measurements of single microbubbles. Each microbubble was modeled as an underdamped linear oscillator to determine the damping ratio and eigenfrequency, and thus the lipid monolayer viscosity and elasticity. Our nonisothermal measurement technique revealed viscoelastic trends for different lipid shell compositions. We observed a significant increase in surface elasticity with the lipid acyl chain length for 16 to 20 carbons, and this effect was explained by an intermolecular forces model that accounts for the lipid composition, packing, and hydration. The surface viscosity was found to be equivalent for these lipid shells. We also observed an anomalous decrease in elasticity and an increase in viscosity when increasing the acyl chain length from 20 to 22 carbons. These results illustrate the use of a novel nondestructive optical technique to investigate lipid monolayer rheology in new regimes of frequency and strain, possibly elucidating the phase behavior, as well as how the dynamic response of a microbubble can be tuned by the lipid intermolecular forces.

  8. Microbubbles are detected prior to larger bubbles following decompression.

    Science.gov (United States)

    Swan, J G; Wilbur, J C; Moodie, K L; Kane, S A; Knaus, D A; Phillips, S D; Beach, T L; Fellows, A M; Magari, P J; Buckey, J C

    2014-04-01

    Using dual-frequency ultrasound (DFU), microbubbles (multiple sites, 2) appear in the presence and absence of bmdVGE, and 3) occur before bmdVGE. This supports the hypothesis that microbubbles precede larger VGE bubbles. Microbubble presence may be an early marker of decompression stress. Since DFU is a low-power ultrasonic method, it may be useful for operational diving applications.

  9. Inferring Characteristics of Sensorimotor Behavior by Quantifying Dynamics of Animal Locomotion

    Science.gov (United States)

    Leung, KaWai

    Locomotion is one of the most well-studied topics in animal behavioral studies. Many fundamental and clinical research make use of the locomotion of an animal model to explore various aspects in sensorimotor behavior. In the past, most of these studies focused on population average of a specific trait due to limitation of data collection and processing power. With recent advance in computer vision and statistical modeling techniques, it is now possible to track and analyze large amounts of behavioral data. In this thesis, I present two projects that aim to infer the characteristics of sensorimotor behavior by quantifying the dynamics of locomotion of nematode Caenorhabditis elegans and fruit fly Drosophila melanogaster, shedding light on statistical dependence between sensing and behavior. In the first project, I investigate the possibility of inferring noxious sensory information from the behavior of Caenorhabditis elegans. I develop a statistical model to infer the heat stimulus level perceived by individual animals from their stereotyped escape responses after stimulation by an IR laser. The model allows quantification of analgesic-like effects of chemical agents or genetic mutations in the worm. At the same time, the method is able to differentiate perturbations of locomotion behavior that are beyond affecting the sensory system. With this model I propose experimental designs that allows statistically significant identification of analgesic-like effects. In the second project, I investigate the relationship of energy budget and stability of locomotion in determining the walking speed distribution of Drosophila melanogaster during aging. The locomotion stability at different age groups is estimated from video recordings using Floquet theory. I calculate the power consumption of different locomotion speed using a biomechanics model. In conclusion, the power consumption, not stability, predicts the locomotion speed distribution at different ages.

  10. Microbubble Distillation for Ethanol-Water Separation

    Directory of Open Access Journals (Sweden)

    Atheer Al-yaqoobi

    2016-01-01

    Full Text Available In the current study, a novel approach for separating ethanol-water mixture by microbubble distillation technology was investigated. Traditional distillation processes require large amounts of energy to raise the liquid to its boiling point to effect removal of volatile components. The concept of microbubble distillation by comparison is to heat the gas phase rather than the liquid phase to achieve separation. The removal of ethanol from the thermally sensitive fermentation broths was taken as a case of study. Consequently the results were then compared with those which could be obtained under equilibrium conditions expected in an “ideal” distillation unit. Microbubble distillation has achieved vapour compositions higher than that which could be obtained under traditional equilibrium conditions. The separation was achieved at liquid temperature significantly less than the boiling point of the mixture. In addition, it was observed that the separation efficiency of the microbubble distillation could be increased by raising the injected air temperature, while the temperature of the liquid mixture increased only moderately. The separation efficiency of microbubble distillation was compared with that of pervaporation for the recovery of bioethanol from the thermally sensitive fermentation broths. The technology could be controlled to give high separation and energy efficiency. This could contribute to improving commercial viability of biofuel production and other coproducts of biorefinery processing.

  11. Photoacoustic radiation force on a microbubble

    Science.gov (United States)

    Erkol, Hakan; Aytac-Kipergil, Esra; Unlu, Mehmet Burcin

    2014-08-01

    We investigate the radiation force on a microbubble due to the photoacoustic wave which is generated by using a pulsed laser. In particular, we focus on the dependence of pulsed laser parameters on the radiation force. In order to do so, we first obtain a new and comprehensive analytical solution to the photoacoustic wave equation based on the Fourier transform for various absorption profiles. Then, we write an expression of the radiation force containing explicit laser parameters, pulse duration, and beamwidth of the laser. Furthermore, we calculate the primary radiation force acting on a microbubble. We show that laser parameters and the position of the microbubble relative to a photoacoustic source have a considerable effect on the primary radiation force. By means of recent developments in laser technologies that render tunability of pulse duration and repetition frequency possible, an adjustable radiation force can be applied to microbubbles. High spatial control of applied force is ensured on account of smaller focal spots achievable by focused optics. In this context, conventional piezoelectric acoustic source applications could be surpassed. In addition, it is possible to increase the radiation force by making source wavelength with the absorption peak of absorber concurrent. The application of photoacoustic radiation force can open a cache of opportunities such as manipulation of microbubbles used as contrast agents and as carrier vehicles for drugs and genes with a desired force along with in vivo applications.

  12. Grafting of abciximab to a microbubble-based ultrasound contrast agent for targeting to platelets expressing GP IIb/IIIa - characterization and in vitro testing.

    Science.gov (United States)

    Della Martina, A; Allémann, E; Bettinger, T; Bussat, P; Lassus, A; Pochon, S; Schneider, M

    2008-03-01

    Abciximab-grafted ultrasound sensitive microbubbles were developed for the diagnosis of stroke. The antibody fragment abciximab, which binds to the GP IIb/IIIa and alpha v beta 3 receptors expressed by activated platelets, was chosen because most ischemic strokes are due to arterial thrombi that are mainly composed of platelets. The abciximab antibody fragment was activated by reduction of the disulfide bond for grafting on the microbubbles. The suspension was freeze-dried after the grafting was performed directly on the formed microbubbles. Quantification of the amounts of abciximab present on the surface of the microbubbles was assessed semi-quantitatively by flow cytometry, and quantitatively using radio-labeled abciximab. A protocol for human and rat platelets deposition and fixation was implemented and the expression of the GP IIb/IIIa receptor was validated by immunostaining. The abciximab-grafted microbubbles showed high static and dynamic binding to fixed platelets. Detection by ultrasonography of microbubbles bound on white and red clots gave higher signals compared to Sono Vue microbubbles.

  13. Acoustically excited encapsulated microbubbles and mitigation of biofouling

    KAUST Repository

    Qamar, Adnan

    2017-08-31

    Provided herein is a universally applicable biofouling mitigation technology using acoustically excited encapsulated microbubbles that disrupt biofilm or biofilm formation. For example, a method of reducing biofilm formation or removing biofilm in a membrane filtration system is provided in which a feed solution comprising encapsulated microbubbles is provided to the membrane under conditions that allow the encapsulated microbubbles to embed in a biofilm. Sonication of the embedded, encapsulated microbubbles disrupts the biofilm. Thus, provided herein is a membrane filtration system for performing the methods and encapsulated microbubbles specifically selected for binding to extracellular polymeric substances (EFS) in a biofilm.

  14. The use of microbubbles to target drug delivery

    Directory of Open Access Journals (Sweden)

    Porter Richard

    2004-11-01

    Full Text Available Abstract Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed.

  15. Quantify Water Extraction by TBP/Dodecane via Molecular Dynamics Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Khomami, Bamin [Univ. of Tennessee, Knoxville, TN (United States); Cui, Shengting [Univ. of Tennessee, Knoxville, TN (United States); de Almeida, Valmor F. [Oak Ridge National Lab., Oak Ridge, TN (United States); Felker, Kevin [Oak Ridge National Lab., Oak Ridge, TN (United States)

    2013-05-16

    The purpose of this project is to quantify the interfacial transport of water into the most prevalent nuclear reprocessing solvent extractant mixture, namely tri-butyl- phosphate (TBP) and dodecane, via massively parallel molecular dynamics simulations on the most powerful machines available for open research. Specifically, we will accomplish this objective by evolving the water/TBP/dodecane system up to 1 ms elapsed time, and validate the simulation results by direct comparison with experimentally measured water solubility in the organic phase. The significance of this effort is to demonstrate for the first time that the combination of emerging simulation tools and state-of-the-art supercomputers can provide quantitative information on par to experimental measurements for solvent extraction systems of relevance to the nuclear fuel cycle. Results: Initially, the isolated single component, and single phase systems were studied followed by the two-phase, multicomponent counterpart. Specifically, the systems we studied were: pure TBP; pure n-dodecane; TBP/n-dodecane mixture; and the complete extraction system: water-TBP/n-dodecane two phase system to gain deep insight into the water extraction process. We have completely achieved our goal of simulating the molecular extraction of water molecules into the TBP/n-dodecane mixture up to the saturation point, and obtained favorable comparison with experimental data. Many insights into fundamental molecular level processes and physics were obtained from the process. Most importantly, we found that the dipole moment of the extracting agent is crucially important in affecting the interface roughness and the extraction rate of water molecules into the organic phase. In addition, we have identified shortcomings in the existing OPLS-AA force field potential for long-chain alkanes. The significance of this force field is that it is supposed to be optimized for molecular liquid simulations. We found that it failed for dodecane and

  16. Quantifying nitrate dynamics in an oligotrophic lake using Δ17O

    Directory of Open Access Journals (Sweden)

    A. Tanaka

    2011-03-01

    Full Text Available The stable isotopic compositions of nitrate, including the 17O anomalies (Δ17O, were determined twice in 1 yr (June and August 2007 in the oligotrophic water column of Lake Mashu, Japan. These data were then used to quantify the geochemical dynamics of nitrate in the lake, by using the deposition rate of the atmospheric nitrate onto the entire catchment area of the lake. The total amount of nitrate in the lake water decreased from 4.2 to 2.1 Mmol during the period between the observations, while the average Δ17O values remained uniform at +2.5‰. The Δ17O values corresponded to an small and uniform mixing ratio of atmospheric nitrate to total nitrate of 9.7 ± 0.8%. These results indicate that 0.52 ± 0.34 Mmol of the remineralized nitrate was fed into the water column through nitrification, while 2.6 ± 0.4 Mmol of nitrate was simultaneously removed from the water column by assimilation, during the period between the observations. The lake water dissolved nitrate was characterized by rapid removal through assimilation during summer until it was almost completely removed from the euphotic layer, as well as continuous feeding into the lake through nitrification (3.2 ± 0.3 Mmol a−1 and deposition (0.35 ± 0.2 Mmol a−1, regardless of the seasons. The 15N-depleted nitrogen isotopic compositions of nitrate were as low as −6.5‰ in June, which also indicates that in-lake nitrification is the major source of nitrate in the lake and suggests that there is low potential for denitrification in and around the lake. Atmospheric nitrate deposited into the lake will be assimilated quickly, having a mean residence time of 1.2 ± 0.1 yr. In addition, more than 90% of the assimilated nitrate will be remineralized to nitrate and re-assimilated via active nitrogen cycling in the lake.

  17. Quantifying sediment dynamics on alluvial fans, Iglesia basin, south Central Argentine Andes

    Science.gov (United States)

    Harries, Rebekah; Kirstein, Linda; Whittaker, Alex; Attal, Mikael; Peralta, Silvio

    2017-04-01

    considering factors such as climate storminess and degree of glacial cover in having a dominant control on the variance of sediment released. These findings have significant implications for our ability to invert the fluvial stratigraphy for climatically driven changes in discharge and highlight a need to quantify the impact of sediment dynamics on modern systems so that we may better understand the limitations in applying quantitative models to ancient stratigraphy.

  18. Therapeutic gas delivery via microbubbles and liposomes.

    Science.gov (United States)

    Fix, Samantha M; Borden, Mark A; Dayton, Paul A

    2015-07-10

    Gaseous molecules including nitric oxide, hydrogen sulfide, carbon monoxide and oxygen mediate numerous cell signaling pathways and have important physiological roles. Several noble gasses have been shown to elicit biological responses. These bioactive gasses hold great therapeutic potential, however, their controlled delivery remains a significant challenge. Recently, researchers have begun using microbubbles and liposomes to encapsulate such gasses for parenteral delivery. The resultant particles are acoustically active, and ultrasound can be used to stimulate and/or image gas release in a targeted region. This review provides a summary of recent advances in therapeutic gas delivery using microbubbles and liposomes.

  19. Noninvasive LV pressure estimation using subharmonic emissions from microbubbles.

    Science.gov (United States)

    Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Raichlen, Joel S; Liu, Ji-Bin; McDonald, Maureen E; Dickie, Kris; Wang, Shumin; Leung, Corina; Forsberg, Flemming

    2012-01-01

    To develop a new noninvasive approach to quantify left ventricular (LV) pressures using subharmonic emissions from microbubbles, an ultrasound scanner was used in pulse inversion grayscale mode; unprocessed radiofrequency data were obtained with pulsed wave Doppler from the aorta and/or LV during Sonazoid infusion. Subharmonic data (in dB) were extracted and processed. Calibration factor (mm Hg/dB) from the aortic pressure was used to estimate LV pressures. Errors ranged from 0.19 to 2.50 mm Hg when estimating pressures using the aortic calibration factor, and were higher (0.64 to 8.98 mm Hg) using a mean aortic calibration factor. Subharmonic emissions from ultrasound contrast agents have the potential to noninvasively monitor LV pressures.

  20. Quantified and applied sea-bed dynamics of the Netherlands Continental Shelf and the Wadden Sea

    NARCIS (Netherlands)

    van Dijk, T.A.G.P.; Kleuskens, M.H.P.; Dorst, L.L.; Van der Tak, C.; Doornenbal, P.J.; Van der Spek, A.J.F.; Hoogendoorn, R.M.; Rodriguez Aguilera, D.; Menninga, P.J.; Noorlandt, R.P.

    2012-01-01

    Sedimentary coasts and shallow-sea beds may be dynamic. The large-scaled spatial variation in these dynamics and the smaller-scaled behaviour of individual marine bedforms are largely unknown. Sea-bed dynamics are relevant for the safety of shipping, and therefore for monitoring strategies, and for

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

    Science.gov (United States)

    Katiyar, Amit; Sarkar, Kausik; Forsberg, Flemming

    2011-04-01

    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.

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

    Science.gov (United States)

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

    2017-03-07

    - 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's 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's 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 fraction. However, all current models and simulations approach 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%, 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.

  3. Three-Dimensional Phenomena in Microbubble Acoustic Streaming

    Science.gov (United States)

    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.

  4. Diagnosing the Dynamics of Observed and Simulated Ecosystem Gross Primary Productivity with Time Causal Information Theory Quantifiers.

    Science.gov (United States)

    Sippel, Sebastian; Lange, Holger; Mahecha, Miguel D; Hauhs, Michael; Bodesheim, Paul; Kaminski, Thomas; Gans, Fabian; Rosso, Osvaldo A

    2016-01-01

    Data analysis and model-data comparisons in the environmental sciences require diagnostic measures that quantify time series dynamics and structure, and are robust to noise in observational data. This paper investigates the temporal dynamics of environmental time series using measures quantifying their information content and complexity. The measures are used to classify natural processes on one hand, and to compare models with observations on the other. The present analysis focuses on the global carbon cycle as an area of research in which model-data integration and comparisons are key to improving our understanding of natural phenomena. We investigate the dynamics of observed and simulated time series of Gross Primary Productivity (GPP), a key variable in terrestrial ecosystems that quantifies ecosystem carbon uptake. However, the dynamics, patterns and magnitudes of GPP time series, both observed and simulated, vary substantially on different temporal and spatial scales. We demonstrate here that information content and complexity, or Information Theory Quantifiers (ITQ) for short, serve as robust and efficient data-analytical and model benchmarking tools for evaluating the temporal structure and dynamical properties of simulated or observed time series at various spatial scales. At continental scale, we compare GPP time series simulated with two models and an observations-based product. This analysis reveals qualitative differences between model evaluation based on ITQ compared to traditional model performance metrics, indicating that good model performance in terms of absolute or relative error does not imply that the dynamics of the observations is captured well. Furthermore, we show, using an ensemble of site-scale measurements obtained from the FLUXNET archive in the Mediterranean, that model-data or model-model mismatches as indicated by ITQ can be attributed to and interpreted as differences in the temporal structure of the respective ecological time

  5. Diagnosing the Dynamics of Observed and Simulated Ecosystem Gross Primary Productivity with Time Causal Information Theory Quantifiers

    Science.gov (United States)

    Sippel, Sebastian; Mahecha, Miguel D.; Hauhs, Michael; Bodesheim, Paul; Kaminski, Thomas; Gans, Fabian; Rosso, Osvaldo A.

    2016-01-01

    Data analysis and model-data comparisons in the environmental sciences require diagnostic measures that quantify time series dynamics and structure, and are robust to noise in observational data. This paper investigates the temporal dynamics of environmental time series using measures quantifying their information content and complexity. The measures are used to classify natural processes on one hand, and to compare models with observations on the other. The present analysis focuses on the global carbon cycle as an area of research in which model-data integration and comparisons are key to improving our understanding of natural phenomena. We investigate the dynamics of observed and simulated time series of Gross Primary Productivity (GPP), a key variable in terrestrial ecosystems that quantifies ecosystem carbon uptake. However, the dynamics, patterns and magnitudes of GPP time series, both observed and simulated, vary substantially on different temporal and spatial scales. We demonstrate here that information content and complexity, or Information Theory Quantifiers (ITQ) for short, serve as robust and efficient data-analytical and model benchmarking tools for evaluating the temporal structure and dynamical properties of simulated or observed time series at various spatial scales. At continental scale, we compare GPP time series simulated with two models and an observations-based product. This analysis reveals qualitative differences between model evaluation based on ITQ compared to traditional model performance metrics, indicating that good model performance in terms of absolute or relative error does not imply that the dynamics of the observations is captured well. Furthermore, we show, using an ensemble of site-scale measurements obtained from the FLUXNET archive in the Mediterranean, that model-data or model-model mismatches as indicated by ITQ can be attributed to and interpreted as differences in the temporal structure of the respective ecological time

  6. Microbubble stability and applications in food

    NARCIS (Netherlands)

    Rovers, T.A.M.

    2015-01-01

    Aeration of food is considered to be a good method to create a texture and mouthfeel of food products that is liked by the consumer. However, traditional foams are not stable for a prolonged time. Microbubbles are air bubbles covered with a shell that slows down disproportionation significantly and

  7. Nonspherical Oscillations of Ultrasound Contrast Agent Microbubbles

    NARCIS (Netherlands)

    Dollet, Benjamin; Meer, van der Sander M.; Garbin, Valeria; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2008-01-01

    The occurrence of nonspherical oscillations (or surface modes) of coated microbubbles, used as ultrasound contrast agents in medical imaging, is investigated using ultra–high-speed optical imaging. Optical tweezers designed to micromanipulate single bubbles in 3-D are used to trap the bubbles far fr

  8. Radionuclide tumor therapy with ultrasound contrast microbubbles

    NARCIS (Netherlands)

    Wamel, van Annemieke; Bouakaz, Ayache; Bernard, Bert; Cate, ten Folkert; Jong, de Nico

    2004-01-01

    Radionuclides have shown to be effective in tumour therapy. However, the side effects determine the maximum deliverable dose. Recently, it has been demonstrated that cells can be permeabilised through sonoporation using ultrasound and contrast microbubbles. The use of sonoporation in treatment of tu

  9. Universal phase and force diagrams for a microbubble or pendant drop in static fluid on a surface

    Science.gov (United States)

    Wei, P. S.; Hsiao, C. C.; Chen, K. Y.

    2008-01-01

    Dimensionless three-dimensional universal phase and lift force diagrams of a microbubble (or pendant drop) in static liquid on a solid surface (or orifice) are presented in this work. Microbubble dynamics has been found to play a vital role in mass, momentum, energy, and concentration transfer rates in contemporary micro- and nanosciences and technologies. In this study, dimensionless phase and force diagrams are introduced by utilizing the analytical solutions of the microbubble shape reported in the literature. It shows that phase and force diagrams can be universally specified by two dimensionless independent parameters, Bond number, and contact angle (or base radius). Based on the presence of an inflection point or neck on the microbubble surface, each diagram exhibits three regions. Growth, detachment, and entrapment of a microbubble can be described by path lines in three regions. The corresponding universal total lift forces include hydrostatic buoyancy, difference in gas, and hydrostatic pressures at the base, capillary pressure, as well as surface tension induced by the variation of circumference, which has not been treated in the literature so far. In the absence of viscous stress and Marangoni force, the total lift force equals surface tension induced by the variation of circumference. The latter can be an attaching or lifting force, depending on whether the state in the distinct regions and contact angle is less than or greater than a critical angle. The critical angle, which is slightly less than the inclination angle at the inflection point, is decreased with increasing Bond number.

  10. A Targeting Microbubble for Ultrasound Molecular Imaging.

    Directory of Open Access Journals (Sweden)

    James Shue-Min Yeh

    Full Text Available Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (streptavidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(streptavidin 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.To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.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.Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i-(iii desired for

  11. A Statistical Physics Characterization of the Complex Systems Dynamics: Quantifying Complexity from Spatio-Temporal Interactions

    OpenAIRE

    Hana Koorehdavoudi; Paul Bogdan

    2016-01-01

    Biological systems are frequently categorized as complex systems due to their capabilities of generating spatio-temporal structures from apparent random decisions. In spite of research on analyzing biological systems, we lack a quantifiable framework for measuring their complexity. To fill this gap, in this paper, we develop a new paradigm to study a collective group of N agents moving and interacting in a three-dimensional space. Our paradigm helps to identify the spatio-temporal states of t...

  12. Perspective: Defining and quantifying the role of dynamics in enzyme catalysis

    Science.gov (United States)

    Warshel, Arieh; Bora, Ram Prasad

    2016-05-01

    Enzymes control chemical reactions that are key to life processes, and allow them to take place on the time scale needed for synchronization between the relevant reaction cycles. In addition to general interest in their biological roles, these proteins present a fundamental scientific puzzle, since the origin of their tremendous catalytic power is still unclear. While many different hypotheses have been put forward to rationalize this, one of the proposals that has become particularly popular in recent years is the idea that dynamical effects contribute to catalysis. Here, we present a critical review of the dynamical idea, considering all reasonable definitions of what does and does not qualify as a dynamical effect. We demonstrate that no dynamical effect (according to these definitions) has ever been experimentally shown to contribute to catalysis. Furthermore, the existence of non-negligible dynamical contributions to catalysis is not supported by consistent theoretical studies. Our review is aimed, in part, at readers with a background in chemical physics and biophysics, and illustrates that despite a substantial body of experimental effort, there has not yet been any study that consistently established a connection between an enzyme's conformational dynamics and a significant increase in the catalytic contribution of the chemical step. We also make the point that the dynamical proposal is not a semantic issue but a well-defined scientific hypothesis with well-defined conclusions.

  13. A generalized framework for quantifying the dynamics of EEG event-related desynchronization.

    Directory of Open Access Journals (Sweden)

    Steven Lemm

    2009-08-01

    Full Text Available Brains were built by evolution to react swiftly to environmental challenges. Thus, sensory stimuli must be processed ad hoc, i.e., independent--to a large extent--from the momentary brain state incidentally prevailing during stimulus occurrence. Accordingly, computational neuroscience strives to model the robust processing of stimuli in the presence of dynamical cortical states. A pivotal feature of ongoing brain activity is the regional predominance of EEG eigenrhythms, such as the occipital alpha or the pericentral mu rhythm, both peaking spectrally at 10 Hz. Here, we establish a novel generalized concept to measure event-related desynchronization (ERD, which allows one to model neural oscillatory dynamics also in the presence of dynamical cortical states. Specifically, we demonstrate that a somatosensory stimulus causes a stereotypic sequence of first an ERD and then an ensuing amplitude overshoot (event-related synchronization, which at a dynamical cortical state becomes evident only if the natural relaxation dynamics of unperturbed EEG rhythms is utilized as reference dynamics. Moreover, this computational approach also encompasses the more general notion of a "conditional ERD," through which candidate explanatory variables can be scrutinized with regard to their possible impact on a particular oscillatory dynamics under study. Thus, the generalized ERD represents a powerful novel analysis tool for extending our understanding of inter-trial variability of evoked responses and therefore the robust processing of environmental stimuli.

  14. Acoustical properties of individual liposome-loaded microbubbles.

    Science.gov (United States)

    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.

  15. Microfluidic fabrication and micromechanics of permeable and impermeable elastomeric microbubbles.

    Science.gov (United States)

    Duncanson, Wynter J; Kodger, Thomas E; Babaee, Sahab; Gonzalez, Grant; Weitz, David A; Bertoldi, Katia

    2015-03-24

    We use droplet microfluidics to produce monodisperse elastomeric microbubbles consisting of gas encapsulated in a polydimethylsiloxane shell. These microbubbles withstand large, repeated deformations without rupture. We perform μN-scale compression tests on individual microbubbles and find their response to be highly dependent on the shell permeability; during deformation, the pressure inside impermeable microbubbles increases, resulting in an exponential increase in the applied force. Finite element models are used to interpret and extend these experimental results enabling the design and development of deformable microbubbles with a predictable mechanical response. Such microbubbles can be designed to repeatedly transit through the narrow constrictions found in a porous medium functioning as probes of the local pressure.

  16. Quantifying the Use of Dynamics in Western Keyboard Music: Lessons and Problems

    Directory of Open Access Journals (Sweden)

    Dorottya Fabian

    2011-01-01

    Full Text Available Ladinig and Huron’s (2010 investigation of the relationship between mode (major-minor and dynamics in Classical and Romantic piano music indicated higher levels of dynamics for compositions from the Classical period but only in major-mode pieces. This was contrary to the expectation that minor mode pieces from the Romantic era would be louder because romantic composers may have intended to convey seriousness, passion or even aggression, rather than sadness. Although the methodology was carefully crafted to enable necessary control for a quantitative study, it also contributed to the questionable relevance of the results. It is arguable whether the chosen repertoire is typical, whether initial markings in the score have a true bearing on the dynamic characteristics of a piece and whether notated dynamics are reliable data due to historical notation conventions and later editorial practices.

  17. Quantifying non-ergodic dynamics of force-free granular gases

    OpenAIRE

    Bodrova, Anna; Chechkin, Aleksei V.; Cherstvy, Andrey G.; Metzler, Ralf

    2015-01-01

    Brownianmotion is ergodic in the Boltzmann–Khinchin sense that long time averages of physical observables such as the mean squared displacement provide the same information as the corresponding ensemble average, even at out-of-equilibrium conditions. This property is the fundamental prerequisite for single particle tracking and its analysis in simple liquids. We study analytically and by event-driven molecular dynamics simulations the dynamics of force-free cooling granular gases and reveal a...

  18. Quantifying the Type of Urban Sprawl and Dynamic Changes in Shenzhen

    OpenAIRE

    Hao, Ruifang; Su, Wei; Yu, Deyong

    2012-01-01

    International audience; Urban sprawl is a hot topic of global concern with increasing dramatically and impact on ecological environment. But there is not a mature method to explain the detail of process of urban sprawl and dynamic changes. In this paper, the dynamic changes of urban is studied based on 1980, 1988, 1994, 2000 and 2005 five remote sensing images of Shenzhen. It is distinguished three types including infilling, edge-expansion and outlying using six landscape metrics related to c...

  19. Microbubble oscillating in a microvessel filled with viscous fluid: A finite element modeling study.

    Science.gov (United States)

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

    2016-03-01

    Understanding the dynamics of coated-microbubble oscillating in an elastic microvessel is important for effective and safe applications of ultrasound contrast agents (UCAs) in imaging and therapy. Numerical simulations are performed based on a two-dimensional (2D) asymmetric finite element model to investigate the influences of both acoustic driving parameters (e.g., pressure and frequency) and material properties (vessel size, microbubble shell visco-elastic parameters and fluid viscosity) on the dynamic interactions in the bubble-blood-vessel system. The results show that, the constrained effect of the blood vessel along the radial direction will induce the asymmetric bubble oscillation and vessel deformation, as well as shifting the bubble resonance frequency toward the higher frequency range. For a bubble (1.5-μm radius) activated by 1-MHz ultrasound pulses in a microvessel with a radius varying between 2 and 6.5 μm, up to 26.95 kPa shear stress could be generated on the vessel wall at a driving pressure of 0.2 MPa, which should be high enough to damage the vascular endothelial cells. The asymmetrical oscillation ratio of the bubble can be aggravated from 0.12% to 79.94% with the increasing acoustic driving pressure and blood viscosity, or the decreasing vessel size and microbubble shell visco-elastic properties. The maximum compression velocity on the bubble shell will be enhanced from 0.19 to 22.79 m/s by the increasing vessel size and acoustic pressure, or the decreasing microbubble shell visco-elasticity and blood viscosity. As the results, the peak values of microstreaming-induced shear stress on the vessel wall increases from 0.003 to 26.95 kPa and the deformation degree of vessel is raised from 1.01 to 1.49, due to the enhanced acoustic amplitude, or the decreasing vessel size, blood viscosity and microbubble shell visco-elasticity. Moreover, it also suggests that, among above impact parameters, microbubble resonance frequency and UCA shell elasticity

  20. Effect of secondary radiation force on aggregation between encapsulated microbubbles

    Institute of Scientific and Technical Information of China (English)

    Zhang Yan-Li; Zheng Hai-Rng; Tang Meng-Xing; Zhang Dong

    2011-01-01

    Secondary radiation force can be an attractive force causing aggregates of encapsulated microbubbles in ultrasonic molecular imaging. The influence of the secondary radiation force on aggregation between two coated bubbles is investigated in this study. Numerical calculations are performed based on four simultaneous differential equations of radial and translational motions.Results show that the secondary force can change from attraction to repulsion during approach,and stable microbubble pairs can be formed in the vicinity of resonant regions; the possibility of microbubble aggregations can be reduced by using low exciting amplitude,ultrasonic frequencies deviating from the resonant frequencies or microbubbles with small compressibility.

  1. A Statistical Physics Characterization of the Complex Systems Dynamics: Quantifying Complexity from Spatio-Temporal Interactions

    Science.gov (United States)

    Koorehdavoudi, Hana; Bogdan, Paul

    2016-06-01

    Biological systems are frequently categorized as complex systems due to their capabilities of generating spatio-temporal structures from apparent random decisions. In spite of research on analyzing biological systems, we lack a quantifiable framework for measuring their complexity. To fill this gap, in this paper, we develop a new paradigm to study a collective group of N agents moving and interacting in a three-dimensional space. Our paradigm helps to identify the spatio-temporal states of the motion of the group and their associated transition probabilities. This framework enables the estimation of the free energy landscape corresponding to the identified states. Based on the energy landscape, we quantify missing information, emergence, self-organization and complexity for a collective motion. We show that the collective motion of the group of agents evolves to reach the most probable state with relatively lowest energy level and lowest missing information compared to other possible states. Our analysis demonstrates that the natural group of animals exhibit a higher degree of emergence, self-organization and complexity over time. Consequently, this algorithm can be integrated into new frameworks to engineer collective motions to achieve certain degrees of emergence, self-organization and complexity.

  2. Theory of microdroplet and microbubble deformation by Gaussian laser beam

    CERN Document Server

    Ellingsen, Simen Å

    2012-01-01

    The theory for linear deformations of fluid microparticles in a laser beam of Gaussian profile is presented, when the beam focus is at the particle center as in optical trapping. Three different fluid systems are considered: water microdroplet in air, air microbubble in water, and a special oil-emulsion in water system used in experiments with optical deformation of fluid interfaces. We compare interface deformations of the three systems when illuminated by a wide (compared to particle radius) and narrow laser beams and analyse differences. Deformations of droplets are radically different from bubbles under otherwise identical conditions, due to the opposite lensing effect (converging and diverging, respectively) of the two; a droplet is deformed far more than a bubble, cetera paribus. Optical contrast is found to be of great importance to the shape obtained when comparing the relatively low-contrast oil-emulsion system to that of water droplets. We finally analyse the dynamics of particle motion when the las...

  3. Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

    DEFF Research Database (Denmark)

    Liu, Y.; Melillo, J.; Niu, S.

    2011-01-01

    Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation...

  4. Quantifying sediment dynamics within the Dutch Wadden Sea using bathymetric monitoring series

    NARCIS (Netherlands)

    Vonhögen-Peeters, L.M.; Heteren, S. van; Wiersma, A.P.; Kleine, M.P.E. de; Marges, V.C.

    2013-01-01

    During the last millennium, human intervention has had an increasing impact on the bathymetry of the Wadden Sea. The significance of these human-induced changes for the decadal-scale development of the Wadden Sea in light of natural sediment dynamics is still unknown. We compared a series of 20 th-c

  5. Quantifying collective effervescence: Heart-rate dynamics at a fire-walking ritual

    DEFF Research Database (Denmark)

    Xygalatas, Dimitris; Konvalinka, Ivana; Roepstorff, Andreas

    2011-01-01

    solidarity, yet quantitative evidence for these conjectures is scarce. Our recent study measured the physiological effects of a highly arousing Spanish fire-walking ritual, revealing shared patterns in heart-rate dynamics between participants and related spectators. We briefly describe our results...

  6. Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

    Directory of Open Access Journals (Sweden)

    María S. Aymerich

    2011-01-01

    Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

  7. Agent-Based Model to Study and Quantify the Evolution Dynamics of Android Malware Infection

    Directory of Open Access Journals (Sweden)

    Juan Alegre-Sanahuja

    2014-01-01

    Full Text Available In the last years the number of malware Apps that the users download to their devices has risen. In this paper, we propose an agent-based model to quantify the Android malware infection evolution, modeling the behavior of the users and the different markets where the users may download Apps. The model predicts the number of infected smartphones depending on the type of malware. Additionally, we will estimate the cost that the users should afford when the malware is in their devices. We will be able to analyze which part is more critical: the users, giving indiscriminate permissions to the Apps or not protecting their devices with antivirus software, or the Android platform, due to the vulnerabilities of the Android devices that permit their rooted. We focus on the community of Valencia, Spain, although the obtained results can be extrapolated to other places where the number of Android smartphones remains fairly stable.

  8. Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

    Science.gov (United States)

    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

  9. SYNTHESIS, CHARACTERIZATION AND APPLICATION OF MICROBUBBLES: A REVIEW

    Directory of Open Access Journals (Sweden)

    J.V. Prajapati and Y.K. Agrawal

    2012-06-01

    Full Text Available Microbubbles are bubbles smaller than one millimeter in diameter, but larger than one micrometer. Microbubbles designate air or gas filled microspheres suspended in a liquid carrier phase which generally results from the introduction of air or gas. The liquid phase contains surfactants to control the surface properties as well as stability of the bubble. Microbubbles have an average size less than that of RBC’s i.e., they are capable of penetrating even into the smallest blood capillaries & releasing drugs or genes, incorporated on their surface, under the action of ultrasound. Microbubbles in general have a wide variety of applications. However in the biomedical field these are primarily used as diagnostic agents in combination with ultrasound for molecular imaging of various organs and even tumours. These are also proposed for drug and gene delivery to targeted regions in combination with various ligands. Most of the physicians today prefer imaging with ultrasound in combination with microbubbles compared to other diagnostic techniques for low cost and rapidity. They are used in medical diagnostics as a contrast agent for ultrasound imaging. The gas-filled, e.g., air or perfluorocarbon, microbubbles oscillate and vibrate when a sonic energy field is applied and may reflect ultrasound waves. This distinguishes the microbubbles from surrounding tissues. 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. In practice, because gas bubbles in liquid lack stability and would therefore quickly dissolve; microbubbles must be encapsulated with a solid shell. The shell is made from either a lipid or a protein such as Optison-microbubbles which consist of perfluoropropane gas encapsulated by a serum albumin shell. Microbubbles may also be used for drug delivery and water/waste water treatment purposes.

  10. EpiTools: An Open-Source Image Analysis Toolkit for Quantifying Epithelial Growth Dynamics.

    Science.gov (United States)

    Heller, Davide; Hoppe, Andreas; Restrepo, Simon; Gatti, Lorenzo; Tournier, Alexander L; Tapon, Nicolas; Basler, Konrad; Mao, Yanlan

    2016-01-11

    Epithelia grow and undergo extensive rearrangements to achieve their final size and shape. Imaging the dynamics of tissue growth and morphogenesis is now possible with advances in time-lapse microscopy, but a true understanding of their complexities is limited by automated image analysis tools to extract quantitative data. To overcome such limitations, we have designed a new open-source image analysis toolkit called EpiTools. It provides user-friendly graphical user interfaces for accurately segmenting and tracking the contours of cell membrane signals obtained from 4D confocal imaging. It is designed for a broad audience, especially biologists with no computer-science background. Quantitative data extraction is integrated into a larger bioimaging platform, Icy, to increase the visibility and usability of our tools. We demonstrate the usefulness of EpiTools by analyzing Drosophila wing imaginal disc growth, revealing previously overlooked properties of this dynamic tissue, such as the patterns of cellular rearrangements.

  11. Exploiting Oceanic Residual Depth to Quantify Present-day Dynamic Topography at the Earth's Surface

    Science.gov (United States)

    Hoggard, Mark; White, Nicky

    2014-05-01

    Convective circulation within the mantle causes vertical motions at the Earth's surface. This dynamic topography is time dependent and occurs on wavelengths of 1000s km with maximum amplitudes of ±2 km. Convective simulation models have been used extensively to make predictions of dynamic topography and have thus far out-paced observational constraints. Here, the well-established relationship between seafloor subsidence and age is used to produce a global map of residual depth anomalies in the oceanic realm. Care is taken to remove other causes of topography, including an isostatic correction for sedimentary loading that takes compaction into account, a correction for variable oceanic crustal thickness, and lithospheric thickening with age away from mid-ocean ridge spreading centres. A dataset including over 1000 seismic reflection profiles and 300 modern wide-angle refraction experiments has been amassed, primarily on old ocean floor adjacent to the continents. Calculation of residual depth yields a map of present-day dynamic topography with amplitudes significantly larger than the errors associated with the corrections. One of the most interesting results occurs along the west coast of Africa, where two full 2000 km wavelengths of dynamic topography have been captured with amplitudes ±1 km that correlate well with the long-wavelength free air gravity anomaly. Comparison with predictive models reveal poor to moderate correlations. This is a direct result of the limited resolution of the mantle tomography models used to set-up convection simulations and also the currently poor understanding of viscosity structure within the Earth. It is hoped that this residual depth dataset should provide an excellent surface boundary constraint for future convective simulation.

  12. Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability.

    Science.gov (United States)

    Zhong, Yuru; Jan, Kung-Ming; Ju, Ki Hwan; Chon, Ki H

    2006-09-01

    The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity (P=0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity (Pparasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.

  13. Quantifying non-ergodic dynamics of force-free granular gases.

    Science.gov (United States)

    Bodrova, Anna; Chechkin, Aleksei V; Cherstvy, Andrey G; Metzler, Ralf

    2015-09-14

    Brownian motion is ergodic in the Boltzmann-Khinchin sense that long time averages of physical observables such as the mean squared displacement provide the same information as the corresponding ensemble average, even at out-of-equilibrium conditions. This property is the fundamental prerequisite for single particle tracking and its analysis in simple liquids. We study analytically and by event-driven molecular dynamics simulations the dynamics of force-free cooling granular gases and reveal a violation of ergodicity in this Boltzmann-Khinchin sense as well as distinct ageing of the system. Such granular gases comprise materials such as dilute gases of stones, sand, various types of powders, or large molecules, and their mixtures are ubiquitous in Nature and technology, in particular in Space. We treat-depending on the physical-chemical properties of the inter-particle interaction upon their pair collisions-both a constant and a velocity-dependent (viscoelastic) restitution coefficient ε. Moreover we compare the granular gas dynamics with an effective single particle stochastic model based on an underdamped Langevin equation with time dependent diffusivity. We find that both models share the same behaviour of the ensemble mean squared displacement (MSD) and the velocity correlations in the limit of weak dissipation. Qualitatively, the reported non-ergodic behaviour is generic for granular gases with any realistic dependence of ε on the impact velocity of particles.

  14. Quantifying Network Dynamics and Information Flow Across Chinese Social Media During the African Ebola Outbreak.

    Science.gov (United States)

    Feng, Shihui; Hossain, Liaquat; Crawford, John W; Bossomaier, Terry

    2017-08-01

    Social media provides us with a new platform on which to explore how the public responds to disasters and, of particular importance, how they respond to the emergence of infectious diseases such as Ebola. Provided it is appropriately informed, social media offers a potentially powerful means of supporting both early detection and effective containment of communicable diseases, which is essential for improving disaster medicine and public health preparedness. The 2014 West African Ebola outbreak is a particularly relevant contemporary case study on account of the large number of annual arrivals from Africa, including Chinese employees engaged in projects in Africa. Weibo (Weibo Corp, Beijing, China) is China's most popular social media platform, with more than 2 billion users and over 300 million daily posts, and offers great opportunity to monitor early detection and promotion of public health awareness. We present a proof-of-concept study of a subset of Weibo posts during the outbreak demonstrating potential and identifying priorities for improving the efficacy and accuracy of information dissemination. We quantify the evolution of the social network topology within Weibo relating to the efficacy of information sharing. We show how relatively few nodes in the network can have a dominant influence over both the quality and quantity of the information shared. These findings make an important contribution to disaster medicine and public health preparedness from theoretical and methodological perspectives for dealing with epidemics. (Disaster Med Public Health Preparedness. 2017;page 1 of 12).

  15. Linear and nonlinear characterization of microbubbles and tissue using the Nakagami statistical model.

    Science.gov (United States)

    Bahbah, N; Novell, A; Bouakaz, A; Djelouah, H

    2017-04-01

    The goal of this work is to exploit the statistical signatures for discrimination between biological tissues and contrast microbubbles in order to develop new strategies for contrast imaging and tissue characterization. For this purpose, the efficiency of the Nakagami statistical model, for describing the ultrasonic echoes of both contrast microbubbles and tissues, was investigated. Experimental measurements have been performed using a linear array probe connected to an open research platform. A commercially available in vitro phantom was used to mimic biological tissue in which SonoVue contrast microbubbles were flowing. Experimental ultrasound echoes have been filtered around the transmitted frequency (fundamental at 2.5MHz) and around twice the transmitted frequency (at 5MHz) for 2nd harmonic analysis, and a logarithmic compression was applied. The signals have been analyzed in order to evaluate the Nakagami parameter m, the scaling parameter Ω and the probability density function at both frequencies. Parametric images based on the Nakagami parameters map (Nakagami-mode images) were reconstructed and compared to B-mode images. Contrary to the B-mode image which is influenced by the system settings and user operations, the Nakagami parametric image is only based on the backscattered statistics of the ultrasonic signals in a local phantom. Such an imaging principle allows the Nakagami image to quantify the local scatterer concentrations in the phantom and to extract the backscattering information from the regions of the weakest echoes that may be lost in the conventional B-mode image. Results show that the tissue and microbubbles characterization is more sensitive in the 2nd harmonic mode when a logarithmic transform is used. These results would be useful for improving the ultrasound image quality and contrast detection in nonlinear mode.

  16. Quantifying the behavior of price dynamics at opening time in stock market

    Science.gov (United States)

    Ochiai, Tomoshiro; Takada, Hideyuki; Nacher, Jose C.

    2014-11-01

    The availability of huge volume of financial data has offered the possibility for understanding the markets as a complex system characterized by several stylized facts. Here we first show that the time evolution of the Japan’s Nikkei stock average index (Nikkei 225) futures follows the resistance and breaking-acceleration effects when the complete time series data is analyzed. However, in stock markets there are periods where no regular trades occur between the close of the market on one day and the next day’s open. To examine these time gaps we decompose the time series data into opening time and intermediate time. Our analysis indicates that for the intermediate time, both the resistance and the breaking-acceleration effects are still observed. However, for the opening time there are almost no resistance and breaking-acceleration effects, and volatility is always constantly high. These findings highlight unique dynamic differences between stock markets and forex market and suggest that current risk management strategies may need to be revised to address the absence of these dynamic effects at the opening time.

  17. History force on coated microbubbles propelled by ultrasound

    NARCIS (Netherlands)

    Garbin, Valeria; Dollet, Benjamin; Overvelde, Marlies; Cojoc, Dan; Di Fabrizio, Enzo; Wijngaarden, van Leen; Prosperetti, Andrea; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2009-01-01

    In this paper the unsteady translation of coated microbubbles propelled by acoustic radiation force is studied experimentally. A system of two pulsating microbubbles of the type used as contrast agent in ultrasound medical imaging is considered, which attract each other as a result of the secondary

  18. The acoustic signature of decaying resonant phospholipid microbubbles

    Science.gov (United States)

    Thomas, D. H.; Butler, M.; Pelekasis, N.; Anderson, T.; Stride, E.; Sboros, V.

    2013-02-01

    Sub-capillary sized microbubbles offer improved techniques for diagnosis and therapy of vascular related disease using ultrasound. Their physical interaction with ultrasound remains an active research field that aims to optimize techniques. The aim of this study is to investigate whether controlled microbubble disruption upon exposure to consecutive ultrasound exposures can be achieved. Single lipid-shelled microbubble scattered echoes have been measured in response to two consecutive imaging pulses, using a calibrated micro-acoustic system. The nonlinear evolution of microbubble echoes provides an exact signature above and below primary and secondary resonance, which has been identified using theoretical results based on the Mooney-Rivlin strain softening shell model. Decaying microbubbles follow an irreversible trajectory through the resonance peak, causing the evolution of specific microbubble spectral signatures. The characteristics of the microbubble motion causes varying amounts of shell material to be lost during microbubble decay. Incident ultrasound field parameters can thus accurately manipulate the regulated shedding of shell material, which has applications for both imaging applications and localized drug delivery strategies.

  19. Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

    Sijl, Jeroen; Dollet, Benjamin; Overvelde, Marlies; Garbin, Valeria; Rozendal, Timo; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2010-01-01

    Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subh

  20. Sonication–Microfluidics for Fabrication of Nanoparticle-Stabilized Microbubbles

    NARCIS (Netherlands)

    Chen, H.; Li, J.; Zhou, W.; Pelan, E.G.; Stoyanov, S.D.; Arnaudov, L.N.; Stone, H.A.

    2014-01-01

    An approach based upon sonication–microfluidics is presented to fabricate nanoparticle-coated microbubbles. The gas-in-liquid slug flow formed in a microchannel is subjected to ultrasound, leading to cavitation at the gas–liquid interface. Therefore, microbubbles are formed and then stabilized by th

  1. Quantifying dynamic changes in plantar pressure gradient in diabetics with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Chi-Wen Lung

    2016-07-01

    Full Text Available Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP and peak pressure gradient (PPG during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking, and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG and PGA were calculated for four foot regions - 1st toe (T1, 1st metatarsal head (M1, 2nd metatarsal head (M2, and heel (HL. Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared to non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P=0.02 and PPG was 214% (P<0.001 larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P=0.04, suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers.

  2. Quantifying Dynamic Changes in Plantar Pressure Gradient in Diabetics with Peripheral Neuropathy

    Science.gov (United States)

    Lung, Chi-Wen; Hsiao-Wecksler, Elizabeth T.; Burns, Stephanie; Lin, Fang; Jan, Yih-Kuen

    2016-01-01

    Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP) and peak pressure gradient (PPG) during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA) has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG, and PGA were calculated for four foot regions – first toe (T1), first metatarsal head (M1), second metatarsal head (M2), and heel (HL). Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared with non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P = 0.02) and PPG was 214% (P < 0.001) larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P = 0.04), suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers. PMID:27486576

  3. Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

    Directory of Open Access Journals (Sweden)

    Assaf Zaritsky

    Full Text Available Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional

  4. Cordilleran forest scaling dynamics and disturbance regimes quantified by aerial lidar

    Science.gov (United States)

    Swetnam, Tyson L.

    Semi-arid forests are in a period of rapid transition as a result of unprecedented landscape scale fires, insect outbreaks, drought, and anthropogenic land use practices. Understanding how historically episodic disturbances led to coherent forest structural and spatial patterns that promoted resilience and resistance is a critical part of addressing change. Here my coauthors and I apply metabolic scaling theory (MST) to examine scaling behavior and structural patterns of semi-arid conifer forests in Arizona and New Mexico. We conceptualize a linkage to mechanistic drivers of forest assembly that incorporates the effects of low-intensity disturbance, and physiologic and resource limitations as an extension of MST. We use both aerial LiDAR data and field observations to quantify changes in forest structure from the sub-meter to landscape scales. We found: (1) semi-arid forest structure exhibits MST-predicted behaviors regardless of disturbance and that MST can help to quantitatively measure the level of disturbance intensity in a forest, (2) the application of a power law to a forest overstory frequency distribution can help predict understory presence/absence, (3) local indicators of spatial association can help to define first order effects (e.g. topographic changes) and map where recent disturbances (e.g. logging and fire) have altered forest structure. Lastly, we produced a comprehensive set of above-ground biomass and carbon models for five distinct forest types and ten common species of the southwestern US that are meant for use in aerial LiDAR forest inventory projects. This dissertation presents both a conceptual framework and applications for investigating local scales (stands of trees) up to entire ecosystems for diagnosis of current carbon balances, levels of departure from historical norms, and ecological stability. These tools and models will become more important as we prepare our ecosystems for a future characterized by increased climatic variability

  5. Two worlds collide: image analysis methods for quantifying structural variation in cluster molecular dynamics.

    Science.gov (United States)

    Steenbergen, K G; Gaston, N

    2014-02-14

    Inspired by methods of remote sensing image analysis, we analyze structural variation in cluster molecular dynamics (MD) simulations through a unique application of the principal component analysis (PCA) and Pearson Correlation Coefficient (PCC). The PCA analysis characterizes the geometric shape of the cluster structure at each time step, yielding a detailed and quantitative measure of structural stability and variation at finite temperature. Our PCC analysis captures bond structure variation in MD, which can be used to both supplement the PCA analysis as well as compare bond patterns between different cluster sizes. Relying only on atomic position data, without requirement for a priori structural input, PCA and PCC can be used to analyze both classical and ab initio MD simulations for any cluster composition or electronic configuration. Taken together, these statistical tools represent powerful new techniques for quantitative structural characterization and isomer identification in cluster MD.

  6. Quantifying and Modelling Long Term Sediment Dynamics in Catchments in Western Europe

    Science.gov (United States)

    Notebaert, B.; De Brue, H.; Verstraeten, G.; Broothaerts, N.

    2015-12-01

    Quantification of sediment dynamics allows to get insight in driving forces and internal dynamics of the sediment cascade system. A useful tool to achieve this is the sediment budget approach, which encompasses the quantification of different sinks and sources. A Holocene time-differentiated sediment budget has been constructed for the Belgian Dijle River catchment (720 km²), based on a large set of field data. The results show how soil erosion is driven by land use changes over longer timescales. Sediment redistribution and the relative importance of the different sinks also vary over time, mainly as a result of changing land use and related landscape connectivity. However, the coarse temporal resolution typically associated with Holocene studies complicates the understanding of sub-millennial scale processes. In a second step, the field-based sediment budget was combined with a modeling approach using Watem/Sedem, a spatially distributed model that simulates soil erosion and colluvial deposition. After validation of the model calibration against the sediment budget, the model was used in a sensitivity analysis. Results confirm the overwhelming influence of human land use on both soil erosion and landscape connectivity, whereas the climatic impact is comparatively small. In addition to catchment-wide simulations, the model also served to test the relative importance of lynchets and dry valleys in different environments. Finally, the geomorphic model was used to simulate past land use, taking into account equifinality. For this purpose, a large series of hypothetical time-independent land use maps of the Dijle catchment were modeled based on a multi-objective allocation algorithm, and applied in Watem/Sedem. Modeled soil erosion and sediment deposition outcomes for each scenario were subsequently compared with the field-based record, taking into account uncertainties. As such, the model allows to evaluate and select realistic land use scenarios for the Holocene.

  7. Quantifying Thermal Disorder in Metal–Organic Frameworks: Lattice Dynamics and Molecular Dynamics Simulations of Hybrid Formate Perovskites

    Science.gov (United States)

    2016-01-01

    Hybrid organic–inorganic materials are mechanically soft, leading to large thermoelastic effects which can affect properties such as electronic structure and ferroelectric ordering. Here we use a combination of ab initio lattice dynamics and molecular dynamics to study the finite temperature behavior of the hydrazinium and guanidinium formate perovskites, [NH2NH3][Zn(CHO2)3] and [C(NH2)3][Zn(CHO2)3]. Thermal displacement parameters and ellipsoids computed from the phonons and from molecular dynamics trajectories are found to be in good agreement. The hydrazinium compound is ferroelectric at low temperatures, with a calculated spontaneous polarization of 2.6 μC cm–2, but the thermal movement of the cation leads to variations in the instantaneous polarization and eventually breakdown of the ferroelectric order. Contrary to this the guanidinium cation is found to be stationary at all temperatures; however, the movement of the cage atoms leads to variations in the electronic structure and a renormalization in the bandgap from 6.29 eV at 0 K to an average of 5.96 eV at 300 K. We conclude that accounting for temperature is necessary for quantitative modeling of the physical properties of metal–organic frameworks. PMID:28298951

  8. Ultrasound triggered drug delivery with liposomal nested microbubbles.

    Science.gov (United States)

    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).

  9. Quantifying sediment dynamics over century and event timescales with Beryllium-10 and Lead-210

    Science.gov (United States)

    Belmont, P.; Willenbring, J.; Schottler, S.

    2010-12-01

    Landscape erosion is unsteady and non-uniform over human timescales. Quantifying that spatial and temporal variability is important for developing an accurate understanding of watershed erosion, as well as useful morphodynamic models that consider erosion, storage, and sediment transport pathways through watersheds. In this study, we have utilized naturally occurring meteoric 10Be and 210Pb to constrain long-term erosion rates and determine the relative importance of different sediment sources in the Le Sueur River watershed, southern Minnesota. Consistently high suspended sediment loads measured in the Le Sueur are the combined result of natural and human-induced processes. Catastrophic baselevel fall of 70 meters that occurred 13,400 years ago initiated rapid river incision with a knickpoint that has propagated 40 km up through the channel network. Over the past 150 years, agriculture has changed the vegetation cover, disturbed soils and profoundly altered watershed hydrology. Primary sediment sources include upland agricultural fields, bluffs and ravines that have resulted from Holocene river incision, and degrading banks and floodplains. Our two tracers provide complementary pieces of information to constrain erosion rates and identify sources. Both tracers exhibit high concentrations in upland soils and low concentrations in bluffs and ravines. Sediment temporarily stored in floodplains is diminished in 210Pb and enriched in 10Be concentration, which allows us to constrain the rate of channel-floodplain exchange. Results from 10Be analysis in the watershed and in the sedimentary record of Lake Pepin, a natural sediment trap downstream, suggest that agriculture has increased landscape erosion rates significantly, but that the relative magnitude of upland erosion compared to other sources has changed over time, with upland contributions being most pronounced in the mid-20th century. Suspended sediment samples analyzed for 10Be and 210Pb from different locations

  10. 13C- and 15N-Labeling Strategies Combined with Mass Spectrometry Comprehensively Quantify Phospholipid Dynamics in C. elegans.

    Directory of Open Access Journals (Sweden)

    Blair C R Dancy

    Full Text Available Membranes define cellular and organelle boundaries, a function that is critical to all living systems. Like other biomolecules, membrane lipids are dynamically maintained, but current methods are extremely limited for monitoring lipid dynamics in living animals. We developed novel strategies in C. elegans combining 13C and 15N stable isotopes with mass spectrometry to directly quantify the replenishment rates of the individual fatty acids and intact phospholipids of the membrane. Using multiple measurements of phospholipid dynamics, we found that the phospholipid pools are replaced rapidly and at rates nearly double the turnover measured for neutral lipid populations. In fact, our analysis shows that the majority of membrane lipids are replaced each day. Furthermore, we found that stearoyl-CoA desaturases (SCDs, critical enzymes in polyunsaturated fatty acid production, play an unexpected role in influencing the overall rates of membrane maintenance as SCD depletion affected the turnover of nearly all membrane lipids. Additionally, the compromised membrane maintenance as defined by LC-MS/MS with SCD RNAi resulted in active phospholipid remodeling that we predict is critical to alleviate the impact of reduced membrane maintenance in these animals. Not only have these combined methodologies identified new facets of the impact of SCDs on the membrane, but they also have great potential to reveal many undiscovered regulators of phospholipid metabolism.

  11. Quantifying the Geomorphic Dynamics of the Extensively Impacted Lower Yuba River

    Science.gov (United States)

    Wyrick, J. R.; Pasternack, G. B.; Carley, J. K.; Barker, R.; Massa, D.; Bratovich, P.; Reedy, G.; Johnson, T.

    2010-12-01

    Traditionally it is has been thought that rivers possess the capability of adjusting their attributes to accommodate varying flow and sediment transport regimes so that sediment in- and out-fluxes are balanced and landform conditions are “stable”. In reality, however, geomorphic drivers and boundary conditions are much more independently dynamic than classically envisioned, such that landforms may always be in a state of adjustment that is normal and appropriate. Rather than thinking of landforms as stable, it is more appropriate to think of them, and the ecosystem services with which they are associated, as resilient in response to change. Knowledge of historic, pre-human baseline conditions or regional reference conditions is limited and may not be as applicable in understanding natural geomorphic and ecosystem services as once envisioned. In light of this natural complexity, a geomorphic assessment of conditions after a large dam or other facility is built and operated may not be as simple as documenting geomorphic instability and attributing that to human impacts relative to the presumed stable baseline conditions. Rather than compare anthropogenically-impacted conditions to theoretical baseline or reference conditions, a more effective approach is to deduce the geomorphic processes in a system under different regimes and evaluate the implications for resiliency of ecosystem services. Through a mechanistic understanding of environmental systems, it may be possible to rationally rehabilitate an ecosystem to achieve resiliency in cases where it has been lost or is desirable to instill, even if it was not historically present. This analytic paradigm is being used to assess the history and on-going geomorphic dynamism of the lower Yuba River (LYR) in northern California. Despite a legacy of massive hydraulic mining waste deposition, dredger re-working of the river valley, dam construction, and flow regulation, the river has been described as lacking the

  12. Correlation between the Quantifiable Parameters of Whole Solitary Pulmonary Nodules Perfusion Imaging Derived with Dynamic CT and Nodules Size

    Directory of Open Access Journals (Sweden)

    Shiyuan LIU

    2009-05-01

    Full Text Available Background and objective The solitary pulmonary nodules (SPNs is one of the most common findings on chest radiographs. The blood flow patterns of the biggest single SPNs level has been studied. This assessment may be only a limited sample of the entire region of interest (ROI and is unrepresentative of the SPNs as a volume. Ideally, SPNs volume perfusion should be measured. The aim of this study is to evaluate the correlation between the quantifiableparameters of SPNs volume perfusion imaging derived with 16-slice spiral CT and 64-slice spiral CT and nodules size. Methods Sixty-five patients with SPNs (diameter≤3 cm; 42 malignant; 12 active inflammatory; 11 benign underwent multi-location dynamic contrast material-enhanced serial CT scanning mode with stable table were performed; The mean values of valid sections were calculated, as the quantifiable parameters of volume SPNs perfusion imaging derived with16-slice spiral CT and 64-slice spiral CT. The correlation between the quantifiable parameters of SPNs volume perfusion imaging derived with 16-slice spiral CT and 64-slice spiral CT and nodules size were assessed by means of linear regression analysis. Results No significant correlations were found between the nodules size and each of the peak height (PHSPN (32.15 Hu±14.55 Hu,ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio(13.20±6.18%, perfusion(PSPN (29.79±19.12 mLmin-1100 g-1 and mean transit time (12.95±6.53 s (r =0.081, P =0.419; r =0.089, P =0.487; r =0.167, P =0.077; r =0.023, P =0.880. Conclusion No significant correlations were found between the quantifiable parameters of SPNs volume perfusion imaging derived with 16-slice spiral CT and 64-slice spiral CT and nodules size.

  13. Quantifying the spatiotemporal dynamics in a chorus frog (Pseudacris) hybrid zone over 30 years.

    Science.gov (United States)

    Engebretsen, Kristin N; Barrow, Lisa N; Rittmeyer, Eric N; Brown, Jeremy M; Moriarty Lemmon, Emily

    2016-07-01

    Although theory suggests that hybrid zones can move or change structure over time, studies supported by direct empirical evidence for these changes are relatively limited. We present a spatiotemporal genetic study of a hybrid zone between Pseudacris nigrita and P. fouquettei across the Pearl River between Louisiana and Mississippi. This hybrid zone was initially characterized in 1980 as a narrow and steep "tension zone," in which hybrid populations were inferior to parentals and were maintained through a balance between selection and dispersal. We reanalyzed historical tissue samples and compared them to samples of recently collected individuals using microsatellites. Clinal analyses indicate that the cline has not shifted in roughly 30 years but has widened significantly. Anthropogenic and natural changes may have affected selective pressure or dispersal, and our results suggest that the zone may no longer best be described as a tension zone. To the best of our knowledge, this study provides the first evidence of significant widening of a hybrid cline but stasis of its center. Continued empirical study of dynamic hybrid zones will provide insight into the forces shaping their structure and the evolutionary potential they possess for the elimination or generation of species.

  14. Using task dynamics to quantify the affordances of throwing for long distance and accuracy.

    Science.gov (United States)

    Wilson, Andrew D; Weightman, Andrew; Bingham, Geoffrey P; Zhu, Qin

    2016-07-01

    In 2 experiments, the current study explored how affordances structure throwing for long distance and accuracy. In Experiment 1, 10 expert throwers (from baseball, softball, and cricket) threw regulation tennis balls to hit a vertically oriented 4 ft × 4 ft target placed at each of 9 locations (3 distances × 3 heights). We measured their release parameters (angle, speed, and height) and showed that they scaled their throws in response to changes in the target's location. We then simulated the projectile motion of the ball and identified a continuous subspace of release parameters that produce hits to each target location. Each subspace describes the affordance of our target to be hit by a tennis ball moving in a projectile motion to the relevant location. The simulated affordance spaces showed how the release parameter combinations required for hits changed with changes in the target location. The experts tracked these changes in their performance and were successful in hitting the targets. We next tested unusual (horizontal) targets that generated correspondingly different affordance subspaces to determine whether the experts would track the affordance to generate successful hits. Do the experts perceive the affordance? They do. In Experiment 2, 5 cricketers threw to hit either vertically or horizontally oriented targets and successfully hit both, exhibiting release parameters located within the requisite affordance subspaces. We advocate a task dynamical approach to the study of affordances as properties of objects and events in the context of tasks as the future of research in this area. (PsycINFO Database Record

  15. Quantifying Transient States in Materials with the Dynamic Transmission Electron Microscope

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, G; LaGrange, T; Kim, J; Reed, B; Browning, N

    2009-09-21

    The Dynamic Transmission Electron Microscope (DTEM) offers a means of capturing rapid evolution in a specimen through in-situ microscopy experiments by allowing 15 ns electron micrograph exposure times. The rapid exposure time is enabled by creating a burst of electrons at the emitter by ultraviolet pulsed laser illumination. This burst arrives a specified time after a second laser initiates the specimen reaction. The timing of the two Q-switched lasers is controlled by high-speed pulse generators with a timing error much less than the pulse duration. Both diffraction and imaging experiments can be performed, just as in a conventional TEM. The brightness of the emitter and the total current control the spatial and temporal resolutions. We have demonstrated 7 nm spatial resolution in single 15 ns pulsed images. These single-pulse imaging experiments have been used to study martensitic transformations, nucleation and crystallization of an amorphous metal, and rapid chemical reactions. Measurements have been performed on these systems that are possible by no other experimental approaches currently available.

  16. Quantifying the impact of woodpecker predation on population dynamics of the emerald ash borer (Agrilus planipennis.

    Directory of Open Access Journals (Sweden)

    David E Jennings

    Full Text Available The emerald ash borer (EAB, Agrilus planipennis, is an invasive beetle that has killed millions of ash trees (Fraxinus spp. since it was accidentally introduced to North America in the 1990s. Understanding how predators such as woodpeckers (Picidae affect the population dynamics of EAB should enable us to more effectively manage the spread of this beetle, and toward this end we combined two experimental approaches to elucidate the relative importance of woodpecker predation on EAB populations. First, we examined wild populations of EAB in ash trees in New York, with each tree having a section screened to exclude woodpeckers. Second, we established experimental cohorts of EAB in ash trees in Maryland, and the cohorts on half of these trees were caged to exclude woodpeckers. The following spring these trees were debarked and the fates of the EAB larvae were determined. We found that trees from which woodpeckers were excluded consistently had significantly lower levels of predation, and that woodpecker predation comprised a greater source of mortality at sites with a more established wild infestation of EAB. Additionally, there was a considerable difference between New York and Maryland in the effect that woodpecker predation had on EAB population growth, suggesting that predation alone may not be a substantial factor in controlling EAB. In our experimental cohorts we also observed that trees from which woodpeckers were excluded had a significantly higher level of parasitism. The lower level of parasitism on EAB larvae found when exposed to woodpeckers has implications for EAB biological control, suggesting that it might be prudent to exclude woodpeckers from trees when attempting to establish parasitoid populations. Future studies may include utilizing EAB larval cohorts with a range of densities to explore the functional response of woodpeckers.

  17. Quantifying the impact of woodpecker predation on population dynamics of the emerald ash borer (Agrilus planipennis).

    Science.gov (United States)

    Jennings, David E; Gould, Juli R; Vandenberg, John D; Duan, Jian J; Shrewsbury, Paula M

    2013-01-01

    The emerald ash borer (EAB), Agrilus planipennis, is an invasive beetle that has killed millions of ash trees (Fraxinus spp.) since it was accidentally introduced to North America in the 1990s. Understanding how predators such as woodpeckers (Picidae) affect the population dynamics of EAB should enable us to more effectively manage the spread of this beetle, and toward this end we combined two experimental approaches to elucidate the relative importance of woodpecker predation on EAB populations. First, we examined wild populations of EAB in ash trees in New York, with each tree having a section screened to exclude woodpeckers. Second, we established experimental cohorts of EAB in ash trees in Maryland, and the cohorts on half of these trees were caged to exclude woodpeckers. The following spring these trees were debarked and the fates of the EAB larvae were determined. We found that trees from which woodpeckers were excluded consistently had significantly lower levels of predation, and that woodpecker predation comprised a greater source of mortality at sites with a more established wild infestation of EAB. Additionally, there was a considerable difference between New York and Maryland in the effect that woodpecker predation had on EAB population growth, suggesting that predation alone may not be a substantial factor in controlling EAB. In our experimental cohorts we also observed that trees from which woodpeckers were excluded had a significantly higher level of parasitism. The lower level of parasitism on EAB larvae found when exposed to woodpeckers has implications for EAB biological control, suggesting that it might be prudent to exclude woodpeckers from trees when attempting to establish parasitoid populations. Future studies may include utilizing EAB larval cohorts with a range of densities to explore the functional response of woodpeckers.

  18. Integrated Analysis of Interferometric SAR, Satellite Altimetry and Hydraulic Modeling to Quantify Louisiana Wetland Dynamics

    Science.gov (United States)

    Lee, Hyongki; Kim, Jin-woo; Lu, Zhong; Jung, Hahn Chul; Shum, C. K.; Alsdorf, Doug

    2012-01-01

    Wetland loss in Louisiana has been accelerating due primarily to anthropogenic and nature processes, and is being advocated as a problem with national importance. Accurate measurement or modeling of wetland-wide water level changes, its varying extent, its storage and discharge changes resulting in part from sediment loads, erosion and subsidence are fundamental to assessment of hurricane-induced flood hazards and wetland ecology. Here, we use innovative method to integrate interferometric SAR (InSAR) and satellite radar altimetry for measuring absolute or geocentric water level changes and applied the methodology to remote areas of swamp forest in coastal Louisiana. Coherence analysis of InSAR pairs suggested that the HH polarization is preferred for this type of observation, and polarimetric analysis can help to identi:fy double-bonnce backscattering areas in the wetland. Envisat radar altimeter-measured 18- Hz (along-track sampling of 417 m) water level data processed with regional stackfile method have been used to provide vertical references for water bodies separated by levees. The high-resolution (approx.40 m) relative water changes measured from ALOS PALSAR L-band and Radarsat-l C-band InSAR are then integrated with Envisat radar altimetry to obtain absolute water level. The resulting water level time series were validated with in situ gauge observations within the swamp forest. Furthermore, we compare our water elevation changes with 2D flood modeling from LISFLOOD hydrodynamic model. Our study demonstrates that this new technique allows retrospective reconstruction and concurrent monitoring of water conditions and flow dynamics in wetlands, especially those lacking gauge networks.

  19. Extracting key information from historical data to quantify the transmission dynamics of smallpox

    Directory of Open Access Journals (Sweden)

    Brockmann Stefan O

    2008-08-01

    Full Text Available Abstract Background Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data. Main findings First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1 The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2 The highest frequency (61.8% of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3 The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions. Conclusion Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.

  20. Quantifying mercury isotope dynamics in captive Pacific bluefin tuna (Thunnus orientalis

    Directory of Open Access Journals (Sweden)

    Sae Yun Kwon

    2016-02-01

    Full Text Available Abstract Analyses of mercury (Hg isotope ratios in fish tissues are used increasingly to infer sources and biogeochemical processes of Hg in natural aquatic ecosystems. Controlled experiments that can couple internal Hg isotope behavior with traditional isotope tracers (δ13C, δ15N can improve the applicability of Hg isotopes as natural ecological tracers. In this study, we investigated changes in Hg isotope ratios (δ202Hg, Δ199Hg during bioaccumulation of natural diets in the pelagic Pacific bluefin tuna (Thunnus orientalis; PBFT. Juvenile PBFT were fed a mixture of natural prey and a dietary supplement (60% Loligo opalescens, 31% Sardinops sagax, 9% gel supplement in captivity for 2914 days, and white muscle tissues were analyzed for Hg isotope ratios and compared to time in captivity and internal turnover of δ13C and δ15N. PBFT muscle tissues equilibrated to Hg isotope ratios of the dietary mixture within ∼700 days, after which we observed a cessation in further shifts in Δ199Hg, and small but significant negative δ202Hg shifts from the dietary mixture. The internal behavior of Δ199Hg is consistent with previous fish studies, which showed an absence of Δ199Hg fractionation during Hg bioaccumulation. The negative δ202Hg shifts can be attributed to either preferential excretion of Hg with higher δ202Hg values or individual variability in captive PBFT feeding preferences and/or consumption rates. The overall internal behavior of Hg isotopes is similar to that described for δ13C and δ15N, though observed Hg turnover was slower compared to carbon and nitrogen. This improved understanding of internal dynamics of Hg isotopes in relation to δ13C and δ15N enhances the applicability of Hg isotope ratios in fish tissues for tracing Hg sources in natural ecosystems.

  1. Methyl mercury dynamics in a tidal wetland quantified using in situ optical measurements

    Science.gov (United States)

    Bergamaschi, B.A.; Fleck, J.A.; Downing, B.D.; Boss, E.; Pellerin, B.; Ganju, N.K.; Schoellhamer, D.H.; Byington, A.A.; Heim, W.A.; Stephenson, M.; Fujii, R.

    2011-01-01

    We assessed monomethylmercury (MeHg) dynamics in a tidal wetland over three seasons using a novel method that employs a combination of in situ optical measurements as concentration proxies. MeHg concentrations measured over a single spring tide were extended to a concentration time series using in situ optical measurements. Tidal fluxes were calculated using modeled concentrations and bi-directional velocities obtained acoustically. The magnitude of the flux was the result of complex interactions of tides, geomorphic features, particle sorption, and random episodic events such as wind storms and precipitation. Correlation of dissolved organic matter quality measurements with timing of MeHg release suggests that MeHg is produced in areas of fluctuating redox and not limited by buildup of sulfide. The wetland was a net source of MeHg to the estuary in all seasons, with particulate flux being much higher than dissolved flux, even though dissolved concentrations were commonly higher. Estimated total MeHg yields out of the wetland were approximately 2.5 μg m−2 yr−1—4–40 times previously published yields—representing a potential loading to the estuary of 80 g yr−1, equivalent to 3% of the river loading. Thus, export from tidal wetlands should be included in mass balance estimates for MeHg loading to estuaries. Also, adequate estimation of loads and the interactions between physical and biogeochemical processes in tidal wetlands might not be possible without long-term, high-frequency in situ measurements.

  2. Formation and dissolution of microbubbles on highly-ordered plasmonic nanopillar arrays

    Science.gov (United States)

    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

  3. Tunable microbubble generator using electrolysis and ultrasound

    Science.gov (United States)

    Achaoui, Younes; Metwally, Khaled; Fouan, Damien; Hammadi, Zoubida; Morin, Roger; Debieu, Eric; Payan, Cédric; Mensah, Serge

    2017-01-01

    This letter reports on a method for producing on demand calibrated bubbles in a non-chemically controlled solution using localized micro-electrolysis and ultrasound. Implementing a feedback loop in the process leads to a point source of stable mono-dispersed microbubbles. This approach overcomes the inertial constraints encountered in microfluidics with the possibility to produce from a single to an array of calibrated bubbles. Moreover, this method avoids the use of additional surfactant that may modify the composition of the host fluid. It impacts across a broad range of scientific domains from bioengineering, sensing to environment.

  4. Tunable microbubble generator using electrolysis and ultrasound

    Directory of Open Access Journals (Sweden)

    Younes Achaoui

    2017-01-01

    Full Text Available This letter reports on a method for producing on demand calibrated bubbles in a non-chemically controlled solution using localized micro-electrolysis and ultrasound. Implementing a feedback loop in the process leads to a point source of stable mono-dispersed microbubbles. This approach overcomes the inertial constraints encountered in microfluidics with the possibility to produce from a single to an array of calibrated bubbles. Moreover, this method avoids the use of additional surfactant that may modify the composition of the host fluid. It impacts across a broad range of scientific domains from bioengineering, sensing to environment.

  5. Acoustic Nonlinear Behaviour of Microbubble Contrast Agent

    Institute of Scientific and Technical Information of China (English)

    俞金飞; 陆荣荣; 龚秀芬; 石涛

    2002-01-01

    We have investigated the nonlinear characteristics of a microbubble contrast agent Sonazoid R (Nycomed,Norway), including the second, third, 1/2-order, 3/2-order and 5/2-order harmonics. We have measured the 1/2-order subharmonic response to different transmission sound pressures. We have found that subharmonic signals cannot be generated until the acoustic pressure reaches a certain value, which is the most different subharmonic from high harmonics. This result is favourable for the further study of the subharmonic in the bubbly liquid.The 3/2-order ultraharmonic response to acoustic pressure was also measured.

  6. Modeling Acoustically Driven Microbubbles by Macroscopic Discrete-Mechanical Analogues

    Directory of Open Access Journals (Sweden)

    Víctor Sánchez-Morcillo

    2013-06-01

    Full Text Available The dynamics of continuous systems that exhibit circular or spherical symmetry like drops, bubbles or some macromolecules, under the influence of some external excitation, develop surface patters that are hard to predict in most practical situations. In the particular case of acoustically driven microbubbles (ultrasound contrast agent, the study of the behavior of the bubble shell requires complex modeling even for describe the most simple oscillation patterns. Furthermore, due to the smallness of the spatio-temporal scale of the problem, an experimental approach requires expensive hardware setup. Despite the complexity of the particular physical problem, the basic dynamical features of some continuous physical systems can be captured by simple models of coupled oscillators. In this work we consider an analogy between a shelled-gas bubble cavitating under the action of an acoustic field and a discrete mechanical system. Thus, we present a theoretical and experimental study of the spatial instabilities of a circular ring of coupled pendulums parametrically driven by a vertical harmonic force. The system is capable of wave propagation and exhibit nonlinearities and dispersion, so manifest rich dynamics: normal oscillation modes (breathing, dipole, quadrupole... and localized patterns of different types (breathers and kinks witch are predicted by finite-differences numerical solutions and observed experimentally. On the basis of this analogy, the oscillation patterns and localized modes observed experimentally in acoustically driven bubbles are interpreted and discussed.

  7. Entropy measures, entropy estimators, and their performance in quantifying complex dynamics: Effects of artifacts, nonstationarity, and long-range correlations

    Science.gov (United States)

    Xiong, Wanting; Faes, Luca; Ivanov, Plamen Ch.

    2017-06-01

    Entropy measures are widely applied to quantify the complexity of dynamical systems in diverse fields. However, the practical application of entropy methods is challenging, due to the variety of entropy measures and estimators and the complexity of real-world time series, including nonstationarities and long-range correlations (LRC). We conduct a systematic study on the performance, bias, and limitations of three basic measures (entropy, conditional entropy, information storage) and three traditionally used estimators (linear, kernel, nearest neighbor). We investigate the dependence of entropy measures on estimator- and process-specific parameters, and we show the effects of three types of nonstationarities due to artifacts (trends, spikes, local variance change) in simulations of stochastic autoregressive processes. We also analyze the impact of LRC on the theoretical and estimated values of entropy measures. Finally, we apply entropy methods on heart rate variability data from subjects in different physiological states and clinical conditions. We find that entropy measures can only differentiate changes of specific types in cardiac dynamics and that appropriate preprocessing is vital for correct estimation and interpretation. Demonstrating the limitations of entropy methods and shedding light on how to mitigate bias and provide correct interpretations of results, this work can serve as a comprehensive reference for the application of entropy methods and the evaluation of existing studies.

  8. Quantifying Grassland-to-Woodland Transitions and the Implications for Carbon and Nitrogen Dynamics in the Southwest United States

    Science.gov (United States)

    Wessman, Carol A.; Archer, Steven R.; Asner, Gregory P.; Bateson, C. Ann

    2004-01-01

    Replacement of grasslands and savannas by shrublands and woodlands has been widely reported in tropical, temperate and high-latitude rangelands worldwide (Archer 1994). These changes in vegetation structure may reflect historical shifts in climate and land use; and are likely to influence biodiversity, productivity, above- and below ground carbon and nitrogen sequestration and biophysical aspects of land surface-atmosphere interactions. The goal of our proposed research is to investigate how changes in the relative abundance of herbaceous and woody vegetation affect carbon and nitrogen dynamics across heterogeneous savannas and shrub/woodlands. By linking actual land-cover composition (derived through spectral mixture analysis of AVIRIS, TM, and AVHRR imagery) with a process-based ecosystem model, we will generate explicit predictions of the C and N storage in plants and soils resulting from changes in vegetation structure. Our specific objectives will be to (1) continue development and test applications of spectral mixture analysis across grassland-to-woodland transitions; (2) quantify temporal changes in plant and soil C and N storage and turnover for remote sensing and process model parameterization and verification; and (3) couple landscape fraction maps to an ecosystem simulation model to observe biogeochemical dynamics under changing landscape structure and climatological forcings.

  9. Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents

    Directory of Open Access Journals (Sweden)

    Shashank R. Sirsi, Mark A. Borden

    2012-01-01

    Full Text Available Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue. The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue. In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1 improving cell membrane permeability, 2 modulate vascular permeability, and 3 enhance endocytotic uptake in cells. Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity. Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery. Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.

  10. Advances in ultrasound mediated gene therapy using microbubble contrast agents.

    Science.gov (United States)

    Sirsi, Shashank R; Borden, Mark A

    2012-01-01

    Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue. The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue. In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1) improving cell membrane permeability, 2) modulate vascular permeability, and 3) enhance endocytotic uptake in cells. Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity. Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery. Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.

  11. Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles.

    Science.gov (United States)

    Sijl, Jeroen; Dollet, Benjamin; Overvelde, Marlies; Garbin, Valeria; Rozendal, Timo; de Jong, Nico; Lohse, Detlef; Versluis, Michel

    2010-11-01

    Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles.

  12. Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting.

    Science.gov (United States)

    Lv, Yongjiu; Hao, Lan; Hu, Wenjing; Ran, Ya; Bai, Yan; Zhang, Liangke

    2016-01-01

    This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated β-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy.

  13. Quantifying spatial and temporal discharge dynamics of an event in a first order stream, using Distributed Temperature Sensing

    Directory of Open Access Journals (Sweden)

    M. C. Westhoff

    2011-03-01

    Full Text Available Understanding spatial distribution of discharge can be important for water quality and quantity modeling. Non-steady flood waves can influence small headwater streams significantly, particularly as a result of short high intensity summer rainstorms. The aim of this paper is to quantify the spatial and temporal dynamics of stream flow in a headwater catchment during a summer rainstorm. These dynamics include gains and losses of stream water, the effect of bypasses that become active and hyporheic exchange fluxes that may vary over time as a function of discharge. We use an advection-dispersion model coupled with an energy balance model to simulate in-stream water temperature, which we confront with high resolution temperature observations obtained with Distributed Temperature Sensing. This model was used as a learning tool to stepwise unravel the complex puzzle of in-stream processes subject to varying discharge. Hypotheses were tested and rejected, which led to more insight in spatial and temporal dynamics in discharge and hyporheic exchange processes. We showed that infiltration losses increase during a rain event, while gains of water remained constant over time. We conclude that, eventually, part of the stream water bypassed the main channel during peak discharge. It also seems that hyporheic exchange varies with varying discharge in the first 250 of the stream; while further downstream it remains constant. Because we relied on solar radiation as the main energy input, we were only able to apply this method during a small event and low flow. However, when additional (artificial energy is available, the presented method is also applicable in larger streams, or during higher flow conditions.

  14. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging

    Science.gov (United States)

    Hsu, Vivian M.; Wes, Ari M.; Tahiri, Youssef; Cornman-Homonoff, Joshua

    2014-01-01

    Background: The aim of this study is to evaluate and quantify dynamic soft-tissue strain in the human face using real-time 3-dimensional imaging technology. Methods: Thirteen subjects (8 women, 5 men) between the ages of 18 and 70 were imaged using a dual-camera system and 3-dimensional optical analysis (ARAMIS, Trilion Quality Systems, Pa.). Each subject was imaged at rest and with the following facial expressions: (1) smile, (2) laughter, (3) surprise, (4) anger, (5) grimace, and (6) pursed lips. The facial strains defining stretch and compression were computed for each subject and compared. Results: The areas of greatest strain were localized to the midface and lower face for all expressions. Subjects over the age of 40 had a statistically significant increase in stretch in the perioral region while lip pursing compared with subjects under the age of 40 (58.4% vs 33.8%, P = 0.015). When specific components of lip pursing were analyzed, there was a significantly greater degree of stretch in the nasolabial fold region in subjects over 40 compared with those under 40 (61.6% vs 32.9%, P = 0.007). Furthermore, we observed a greater degree of asymmetry of strain in the nasolabial fold region in the older age group (18.4% vs 5.4%, P = 0.03). Conclusions: This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time. PMID:25426394

  15. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging.

    Science.gov (United States)

    Hsu, Vivian M; Wes, Ari M; Tahiri, Youssef; Cornman-Homonoff, Joshua; Percec, Ivona

    2014-09-01

    The aim of this study is to evaluate and quantify dynamic soft-tissue strain in the human face using real-time 3-dimensional imaging technology. Thirteen subjects (8 women, 5 men) between the ages of 18 and 70 were imaged using a dual-camera system and 3-dimensional optical analysis (ARAMIS, Trilion Quality Systems, Pa.). Each subject was imaged at rest and with the following facial expressions: (1) smile, (2) laughter, (3) surprise, (4) anger, (5) grimace, and (6) pursed lips. The facial strains defining stretch and compression were computed for each subject and compared. The areas of greatest strain were localized to the midface and lower face for all expressions. Subjects over the age of 40 had a statistically significant increase in stretch in the perioral region while lip pursing compared with subjects under the age of 40 (58.4% vs 33.8%, P = 0.015). When specific components of lip pursing were analyzed, there was a significantly greater degree of stretch in the nasolabial fold region in subjects over 40 compared with those under 40 (61.6% vs 32.9%, P = 0.007). Furthermore, we observed a greater degree of asymmetry of strain in the nasolabial fold region in the older age group (18.4% vs 5.4%, P = 0.03). This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.

  16. Microbubble generation by piezotransducer for biological studies

    Science.gov (United States)

    Zhu, W.; Alkhazal, M.; Cho, M.; Xiao, S.

    2015-12-01

    Bubbles induced by blast waves or shocks are speculated to be the major cause of damages in biological cells in mild traumatic brain injuries. Microbubble collapse was found to induce noticeable cell detachment from the cell substrate, changes in focal adhesion and biomechanics. To better understand the bubble mechanism, we would like to construct a system, which allows us to clearly differentiate the impact of bubbles from that of shocks. Such a generator needs to be low profile in order to place under a microscope. A piezoelectric transducer system was designed to meet the need. The system uses either a flat or a spherical focusing piezoelectric transducer to produce microbubbles in a cuvette loaded with cell-culture medium. The transducer is placed on the side of the cuvette with its axis lining horizontally. A cover slip is placed on the top of the cuvette. The impact of the waves to the cells is minimized as the cover slip is parallel to the direction of the wave. Only bubbles from the medium reach the cover slip and interact with cells. The effect of bubbles therefore can be separated that of pressure waves. The bubbles collected on a cover slip range in size from 100 μm to 10 μm in radius, but the dominant size is 20-30 μm.

  17. Ultrasonic microbubble contrast agents and the transplant kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kay, D.H., E-mail: davidhkay@doctors.org.u [Department of Radiology, Western Infirmary, Glasgow (United Kingdom); Mazonakis, M.; Geddes, C. [Department of Renal Medicine, Western Infirmary, Glasgow (United Kingdom); Baxter, G. [Department of Radiology, Western Infirmary, Glasgow (United Kingdom)

    2009-11-15

    Aim: To evaluate the potential application of microbubble agents in the immediate post-transplant period, by studying contrast uptake and washout, and to correlate these values with clinical indices, and thus, assess the potential prognostic value of this technique. Materials and methods: The study group comprised 20 consecutive renal transplant patients within 7 days of transplantation. Sonovue was administered as an intravenous bolus with continuous imaging of the transplant kidney at low mechanical index (MI) for 1 min post-injection. These data were analysed off-line by two observers, and time intensity curves (TIC) for the upper, mid, and lower poles constructed. Within each pole, a region of interest (5 mm square) was placed over the cortex, medullary pyramid, and interlobar artery, resulting in a total of nine TIC for each patient. TIC parameters included the arrival time (AT), time to peak (TTP), peak intensity (Max), gradient of the slope (M), and the area under curve (AUC). Results: For both observers there was good agreement for all values measured from the cortex and medulla, but poor interobserver correlation for the vascular values. In addition, there was only agreement for these values in the upper and mid-pole of the transplant with poor agreement for the lower pole values. The mid-pole of the transplant kidney was chosen as the point of measurement for subsequent studies. Mid-pole values were correlated with clinical data and outcome over the 3-month post-transplant period. Renal microbubble perfusion correlated with the transplant estimated glomerular filtration rate (eGFR) at 3 months post-transplantation (p = 0.016). Discussion: In conclusion, this is the first study to confirm reproducibility of the Sonovue TIC data in transplant patients and to quantify regional variation and perfusion. The statistically significant estimates of transplant perfusion may be of future benefit to transplant recipients and potentially utilized as a prognostic tool

  18. Jet drops from microbubble rupture

    Science.gov (United States)

    Yu, Yingxian; Bartlett, Casey; Bird, James

    2014-11-01

    When a bubble bursts at an interface, the surface energy creates an upward jet that can break into smaller droplets. Extensive research has demonstrated that the size of the droplets depends on the size of the initial bubbles. Yet this research has almost entirely been conducted for bubbles that are larger than 100 microns. As the bubbles approach 100 microns, the linear relation seems to deviate, although there have not been systematic experiments in this regime - mainly because these smaller bubbles and the even smaller droplets that they create have been difficult to visualize in the past. Here we directly measure the jetting phenomena for bubbles that are smaller than 100 micron using a combination of microfluidics and high-speed photography, and we relate our results to theory. Lab Name: Interfacial Fluidic Dynamics Laboratory Faculty Mentor's Name: James C. Bird.

  19. Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease

    Institute of Scientific and Technical Information of China (English)

    Scott Grier; Adrian KP Lim; Nayna Patel; Jeremy FL Cobbold; Howard C Thomas; Isobel J Cox; Simon D Taylor-Robinson

    2006-01-01

    Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

  20. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

    Science.gov (United States)

    Kishen, Anil; George, Saji

    2013-02-01

    In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

  1. Theragnostic ultrasound using microbubbles in the treatment of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jong; Yoon, Young Il; Bae, Yun Jung [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-08-15

    The use of gas-filled microbubbles in perfusion monitoring as intravascular ultrasound contrast agents has recently become more common. Additionally, microbubbles are employed as carriers of pharmaceutical substances or genes. Microbubbles have great potential to improve the delivery of therapeutic materials into cells and to modify vascular permeability, causing increased extravasation of drugs and drug carriers. Prostate cancer is the most common neoplasm in Europe and America, with an incidence twice to three times that of lung and colorectal cancer. Its incidence is still rising in Asian countries, including Japan and Korea. In this review, we present current strategies regarding the synthesis of microbubbles with targeted ligands on their surfaces, with a focus on prostate cancer.

  2. Algal cell disruption using microbubbles to localize ultrasonic energy.

    Science.gov (United States)

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

    2014-12-01

    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 10(8)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.

  3. Quantifying and Contrasting Spatial and Temporal Dynamics of Vadose Zone Moisture under Different Vegetation Types Using Electrical Resistivity Imaging

    Science.gov (United States)

    Sharma Acharya, B.; Zou, C.; Halihan, T.

    2016-12-01

    Spatial-temporal dynamics of vadose zone moisture is important for assessing deep drainage in water-limited ecosystems. Time-lapse electrical resistivity imaging (ERI) was used to monitor vadose zone moisture to a depth of 9 m in a tallgrass prairie and a prairie heavily encroached by a juniper species (Juniperus virigiana) in the south-central Great Plains, US. Resistivity images were converted to volumetric water content images based on site-specific relationship between volumetric water content and inverted resistivity values. Results show (a) vegetation induced vertical soil moisture profiling in the vadose zone, (b) increased spatial-temporal variability in rooting zone conductivity under juniper-encroached site compared with tallgrass prairie site, and (c) two-layered conductivity profiles irrespective of vegetation types, with increased conductivity below 3 m soil depth. ERI could be used as an effective approach to quantify spatial-temporal variation of vadose zone moisture and time-lapse ERI images can be used to assess deep drainage potential associated with different land cover types in water-limited ecosystems.

  4. Quantifying humpback whale song sequences to understand the dynamics of song exchange at the ocean basin scale.

    Science.gov (United States)

    Garland, Ellen C; Noad, Michael J; Goldizen, Anne W; Lilley, Matthew S; Rekdahl, Melinda L; Garrigue, Claire; Constantine, Rochelle; Daeschler Hauser, Nan; Poole, M Michael; Robbins, Jooke

    2013-01-01

    Humpback whales have a continually evolving vocal sexual display, or "song," that appears to undergo both evolutionary and "revolutionary" change. All males within a population adhere to the current content and arrangement of the song. Populations within an ocean basin share similarities in their songs; this sharing is complex as multiple variations of the song (song types) may be present within a region at any one time. To quantitatively investigate the similarity of song types, songs were compared at both the individual singer and population level using the Levenshtein distance technique and cluster analysis. The highly stereotyped sequences of themes from the songs of 211 individuals from populations within the western and central South Pacific region from 1998 through 2008 were grouped together based on the percentage of song similarity, and compared to qualitatively assigned song types. The analysis produced clusters of highly similar songs that agreed with previous qualitative assignments. Each cluster contained songs from multiple populations and years, confirming the eastward spread of song types and their progressive evolution through the study region. Quantifying song similarity and exchange will assist in understanding broader song dynamics and contribute to the use of vocal displays as population identifiers.

  5. Application of micro-bubbles on oral care.

    Science.gov (United States)

    Lin, Pei-Ju; Chuang, Ming-Chuen; Chang, Szu-Chung

    2017-09-15

    This study proposed a method of using a modified micro-bubble generator with its ejection nozzle connected to an ergonomically designed soft teeth-tray for plaque removal. The applicability of this method was verified and the influence on plaque removal efficacy of some parameters of this device was clarified. The micro-bubble generator used in this study has 5 rotation speed settings, 5 nozzle sizes, and a soft teeth-tray ejection pore diameters. These were used as independent variables to investigate their effect on the ejected flow volume, velocity and micro-bubble dimension, and how they eventually affect the plaque removal efficacy from a denture. When the micro-bubble generator coupled with large (4.8 mm) ejection pore teeth-tray and the largest (1.2 mm) nozzle diameter more than 98% of plaque can be removed; its applicability on cleaning denture can be verified. In general, the larger nozzle diameter and teeth-tray ejection pore diameter will remove more plaques; while the higher the flow velocity and the smaller the micro-bubble of the ejected stream, better cleaning efficacy can be achieved. The application of micro-bubble on plaque removal seems effective, although at this moment it is applied on denture cleaning. The finding of the influence of some critical design parameters of micro-bubble generator and variables of ejected stream can be referred to further design a new micro-bubble cleaner for effective plaque removal from the teeth in human oral cavity.

  6. Quantifying the role of immobile water on pollutant fluxes in double-permeable media under dynamic flow conditions

    Science.gov (United States)

    Knorr, Bastian; Krämer, Florian; Stumpp, Christine; Maloszewski, Piotr

    2014-05-01

    inhibited the back-diffusion from immobile water to mobile water zones. Mathematical models based on analytical and numerical models have to be further developed to describe and quantify these observed processes. A better understanding about the influence of immobile water and dynamic flow conditions on pollutant transport will help to improve prediction of pollutant fluxes and site remediation techniques and management.

  7. Dynamic contrast-enhanced 3-T magnetic resonance imaging: a method for quantifying disease activity in early polyarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Navalho, Marcio [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital da Luz, Radiology Department, Lisbon (Portugal); Hospital da Luz, Centro de Imagiologia, Lisbon (Portugal); Resende, Catarina [Hospital da Luz, Rheumatology Department, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Rodrigues, Ana Maria; Fonseca, Joao Eurico; Canhao, Helena [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Gaspar, Augusto [Hospital da Luz, Radiology Department, Lisbon (Portugal); Campos, Jorge [Hospital de Santa Maria, Radiology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal)

    2012-01-15

    To determine whether measurement of synovial enhancement and thickness quantification parameters with 3.0-Tesla magnetic resonance imaging (3-T MRI) can reliably quantify disease activity in patients with early polyarthritis. Eighteen patients (16 women, 2 men; mean age 46 years) with early polyarthritis with less than 12 months of symptoms were included. MRI examination using 3-T device was performed by a new approach including both wrists and hands simultaneously in the examination field-of-view. MRI scoring of disease activity included quantification of synovial enhancement with simple measurements such as rate of early enhancement (REE; REE{sub 57} = S{sub 57}/S{sub 200}, where S{sub 57} and S{sub 200} are the signal intensities 57 s and 200 s after gadolinium injection) and rate of relative enhancement (RE; RE = S{sub 200} - S{sub 0}). Both wrists and hands were scored according to the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for synovitis. Disease activity was clinically assessed by the 28-joint Disease Activity Score (DAS28). DAS28 score was strongly correlated with RE (r = 0.8331, p < 0.0001), REE (r = 0.8112, p < 0.0001), and RAMRIS score for synovitis (r = 0.7659, p < 0.0002). An REE score above 0.778 accurately identified patients with clinically active disease (sensitivity 92%; specificity 67%; p < 0.05). A statistically significant difference was observed in the RE, REE, and RAMRIS scores for synovitis between patients with active and inactive disease (p < 0.05). Our findings support the use of 3-T dynamic contrast-enhanced MRI for precise quantification of disease activity and for discriminating active disease from inactive disease in early polyarthritis. (orig.)

  8. Quantifying Hyporheic Exchanges in a Large Scale River Reach Using Coupled 3-D Surface and Subsurface Computational Fluid Dynamics Simulations

    Science.gov (United States)

    Bao, J.; Zhou, T.; Huang, M.; Hou, Z.; Perkins, W. A.; Harding, S.; Hammond, G. E.; Ren, H.; Thorne, P. D.; Suffield, S. R.; Zachara, J. M.

    2016-12-01

    Hyporheic exchange between river water and groundwater is an important mechanism for biogeochemical processes, such as carbon and nitrogen cycling, and biodegradation of organic contaminants, in the subsurface interaction zone. The relationship between river flow conditions and hyporheic exchanges therefore is of great interests to hydrologists, biogeochemists, and ecologists. However, quantifying relative influences of hydrostatic and hydrodynamic drivers on hyporheic exchanges is very challenging in large rivers due to accessibility and spatial coverage of measurements, and computational tools available for numerical experiments. In this study, we aim to demonstrate that a high resolution computational fluid dynamics (CFD) model that couples surface and subsurface flow and transport can be used to simulate hyporheic exchanges and the residence time of river water in the hypothetic zone. Base on the assumption that the hyporheic exchange does not affect the surface water flow condition due to its small magnitude compared to the velocity of river water, we developed a one way coupled surface and subsurface water flow model in a commercial CFD software STAR-CCM+, that connects the Reynolds-averaged Navier-Stokes (RANS) equation solver with a realizable two-layer turbulence model, a two-layer all y+ wall treatment, and the volume of fluid (VOF) method for tracking the free water-air interface as well as porous media flow in the subsurface domain. The model is applied to a 7-km long section of the Columbia River and validated against measurements from the acoustic Doppler current profiler (ADCP) in the surface water and hyporheic fluxes derived from a set of temperature profilers installed across the riverbed. The validated model is then employed to systematically investigate how hyporheic exchanges influenced by 1) riverbed properties such as the permeability and thickness of the alluvial layer; 2) surface water hydrodynamics due to channel geomorphological settings

  9. Interaction of an ultrasound-activated contrast microbubble with a wall at arbitrary separation distances

    Science.gov (United States)

    Doinikov, Alexander A.; Bouakaz, Ayache

    2015-10-01

    Both in vitro and in vivo, contrast agent microbubbles move near bounding surfaces, such as the wall of an experimental container or the wall of a blood vessel. This problem inspires interest in theoretical models that predict the effect of a wall on the dynamics of a contrast microbubble. There are models for a bubble at a large distance from a wall and for a bubble adherent to a wall. The aim of the present study is to develop a generalized model that describes the dynamics of a contrast microbubble at arbitrary distances from a wall and thereby make it possible to simulate the acoustic response of the bubble starting from large separation distances up to contact between the bubble and the wall. The wall is assumed to be a plane. Therefore, the developed model applies for in vitro investigations of contrast agents in experimental containers. It can also be used as a first approximation to the case of a contrast microbubble within a large blood vessel. The derivation of the model is based on the multipole expansion of the bubble velocity potential, the image source method, and the Lagrangian formalism. The model consists of two coupled equations, one of which describes the bubble radial oscillation and the second describes the translation of the bubble center. Numerical simulations are performed to determine how the acoustic response of a contrast microbubble depends on the separation distance near walls of different types: rigid, plastic, arterial, etc. The dynamics of the bubble encapsulation is described by the Marmottant shell model. The properties of the plastic wall correspond to OptiCell chambers commonly used in experiments. The results of the simulations show that the bubble resonance frequency near a wall depends on both the separation distance and the wall material properties. In particular, the rigid wall makes the resonance frequency decrease with decreasing separation distance, whereas in the vicinity of the OptiCell wall and the arterial wall, the

  10. Quantifying the spatio-temporal dynamics of woody plant encroachment using an integrative remote sensing, GIS, and spatial modeling approach

    Science.gov (United States)

    Buenemann, Michaela

    Despite a longstanding universal concern about and intensive research into woody plant encroachment (WPE)---the replacement of grasslands by shrub- and woodlands---our accumulated understanding of the process has either not been translated into sustainable rangeland management strategies or with only limited success. In order to increase our scientific insights into WPE, move us one step closer toward the sustainable management of rangelands affected by or vulnerable to the process, and identify needs for a future global research agenda, this dissertation presents an unprecedented critical, qualitative and quantitative assessment of the existing literature on the topic and evaluates the utility of an integrative remote sensing, GIS, and spatial modeling approach for quantifying the spatio-temporal dynamics of WPE. Findings from this research suggest that gaps in our current understanding of WPE and difficulties in devising sustainable rangeland management strategies are in part due to the complex spatio-temporal web of interactions between geoecological and anthropogenic variables involved in the process as well as limitations of presently available data and techniques. However, an in-depth analysis of the published literature also reveals that aforementioned problems are caused by two further crucial factors: the absence of information acquisition and reporting standards and the relative lack of long-term, large-scale, multi-disciplinary research efforts. The methodological framework proposed in this dissertation yields data that are easily standardized according to various criteria and facilitates the integration of spatially explicit data generated by a variety of studies. This framework may thus provide one common ground for scientists from a diversity of fields. Also, it has utility for both research and management. Specifically, this research demonstrates that the application of cutting-edge remote sensing techniques (Multiple Endmember Spectral Mixture

  11. Using seismic arrays to quantify the physics of a glacial outburst flood and its legacy on upland river dynamics

    Science.gov (United States)

    Gimbert, Florent; Cook, Kristen; Andermann, Christoff; Hovius, Niels; Turowski, Jens

    2017-04-01

    In the Himalayas fluvial erosion is thought to be controlled by the intense annual Indian Summer Monsoon precipitation. However, this region is also exposed to catastrophic floods generated by the sudden failure of landslides or moraine dams. These floods are rare and particularly devastating. Thus they have a strong impact on rivers and adjacent hillslopes, and they represent a hazard for local populations. Due to the difficulties to observe these floods and quantify their physics using traditional methods, their importance for the long-term evolution of Himalayan Rivers remains largely unknown, and no consistent early warning system exists to anticipate these events, especially in trans-boundary regions. Here we show that seismic arrays can be used to (i) reliably anticipate outburst floods and to (ii) quantify multiple and key fluvial processes associated with their propagation and their lasting impacts on upland river dynamics. We report unique seismic observations of a glacial lake outburst flood event that occurred the 5th of July 2016 in the Bhote Koshi River (Central Nepal). Precursory seismic signals are identified from the onset of the lake drainage event such that an early warning alarm may be turned on about an hour before the outburst flood wave reaches areas with an exposed population. Using our network of stations we observe for the first time that the outburst flood wave is in fact made of two distinct waves, namely a water flow wave and a bedload sediment wave. As expected these two waves travel at different speeds. We find that the ratio between the two wave speeds matches with that previously found at much smaller scales in flume laboratory experiments. Based on the physical modelling of both water-flow- and bedload- induced seismic noise we provide estimates of flow depth and bedload transport characteristics (flux, moving grains sizes) prior, during and after the flood. In particular we show that bedload sediment flux is enhanced by up to a

  12. Condensation phase diagrams for lipid-coated perfluorobutane microbubbles.

    Science.gov (United States)

    Mountford, Paul A; Sirsi, Shashank R; Borden, Mark A

    2014-06-03

    The goal of this study was to explore the thermodynamic conditions necessary to condense aqueous suspensions of lipid-coated gas-filled microbubbles into metastable liquid-filled nanodrops as well as the physicochemical mechanisms involved with this process. Individual perfluorobutane microbubbles and their lipid shells were observed as they were pressurized at 34.5 kPa s(-1) in a microscopic viewing chamber maintained at temperatures ranging from 5 to 75 °C. The microbubbles contracted under pressure, ultimately leading to either full dissolution or microbubble-to-nanodrop condensation. Temperature-pressure phase diagrams conveying condensation and stability transitions were constructed for microbubbles coated with saturated diacylphosphatidylcholine lipids of varying acyl chain length (C16 to C24). The onset of full dissolution was shifted to higher temperatures with the use of longer acyl chain lipids or supersaturated media. Longer chain lipid shells resisted both dissolution of the gas core and mechanical compression through a pronounced wrinkle-to-fold collapse transition. Interestingly, the lipid shell also provided a mechanical resistance to condensation, shifting the vapor-to-liquid transition to higher pressures than for bulk perfluorobutane. This result indicated that the lipid shell can provide a negative apparent surface tension under compression. Overall, the results of this study will aid in the design and formulation of vaporizable fluorocarbon nanodrops for various applications, such as diagnostic ultrasound imaging, targeted drug delivery, and thermal ablation.

  13. Ultrasound and Microbubbles: Their Functions in Gene Transfer In Vitro

    Institute of Scientific and Technical Information of China (English)

    CHEN Yunchao; HUANG Daozhong; LI Kaiyan; WANG Zhihui; HONG Kai; WANG Fen; ZANG Qingping

    2007-01-01

    To examine the role of ultrasound in gene delivery in vitro, three cells lines were exposed to the low-frequency ultrasound of varying intensities and for different durations to evaluate their effect on gene transfection and cell viability of the cells. Microbubble (MB), Optison (10%), was also used to observe the role of the microbubbles in gene transfection. The results demonstrated that as the ultrasound intensity and the exposure time increased, the gene transfer rate increased and the cell viability decreased, but at high energy intensities, the cell viability decreased dramatically, which caused the transfer rate to decrease. The most efficient ultrasound intensity for inducing gene transfer was 1 W/cm2 with duration being 20 s. At the same energy intensity, higher ultrasound intensity could achieve maximal gene transfer rate earlier. Microbubbles could increase ultrasound-induced cell gene transfer rate by about 2 to 3 times mainly at lower energy intensities. Moreover, microbubbles could raise the maximum gene transfer rate mediated by ultrasound. It is concluded that the low-frequency ultrasound can induce cell gene transfer and the cell gene transfer rate and viability are correlated with not only the ultrasound energy intensity but also the ultrasound intensity, the higher ultrasound intensity achieves its maximal transfer rate more quickly and the ultrasound intensity that can induce optimal gene transfer is 1 W/cm2 with duration being 20 s, and microbubbles can significantly increase the maximal gene transfer rate in vitro.

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

    Science.gov (United States)

    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 (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

  15. Writing with lasers: a new technique of controlled lithography using thermooptically manipulated microbubbles

    Science.gov (United States)

    Ghosh, Subhrokoli; Roy, Basudev; Paul, Shuvojit; Das, Santu; Roy, Soumyajit; Banerjee, Ayan

    2015-06-01

    We have developed a new technique of optical micro-patterning using micro bubbles based on light induced self- assembly of materials using thermo-optic tweezers. Presently, we use a liquid matter- Soft Oxo-Metalate (SOMs) that have high absorption near the wavelength of the tweezers laser at 1064 nm. An aqueous dispersion of the sample solution is taken in a glass sample chamber and introduced into the translation stage of our tweezers set-up (inverted microscope) where a highly focused laser beam is aimed at SOM particles adsorbed on the top surface of the sample chamber. The high absorptivity of SOMs ensures the creation of a local `hot-spot' which leads to the nucleation of a micro-bubble in this region. Thus, a large local surface-tension gradient is introduced in the vicinity of the micro-bubble due to the temperature gradient produced at the two ends of the bubble, which leads to a Marangoni type convective ow around the bubble. This ow causes material to be self-assembled at the base of the bubble. As the translation stage is moved, the `hot-spot' moves simultaneously, and due to the resulting ow dynamics, the microbubble is also translated thus causing continuous accumulation of the SOMs around it. Simultaneously, due to the sudden thermal shock generated when the `hot-spot' is moved away from the self-assembled SOMs, they undergo a phase transition from soft (liquid) to hard (crystalline) state, resulting in the formation of a stable permanent pattern of choice on the glass substrate. This technique can have diverse applications with materials other than SOMs including carbon nano tubes, organic dyes, catalysts and conducting polymers, etc, being co-deposited from aqueous dispersions of the particular material with the SOMs. The patterns thus formed have been used for various applications including the development of catalytic micro-chips, and solution processed printable micro-circuits.

  16. A facile fabrication of alginate microbubbles using a gas foaming reaction.

    Science.gov (United States)

    Huang, Keng-Shiang; Lin, Yung-Sheng; Chang, Wan-Ru; Wang, Yi-Ling; Yang, Chih-Hui

    2013-08-12

    Microbubble particles have been extensively utilized as temporal templates for various biomedical applications. This study proposes a facile strategy to obtain microbubble-containing alginate particles (i.e., microbubbles inside alginate gel particles, called alginate microbubbles). The chemical reaction of sodium bicarbonate and hydrogen peroxide to produce gaseous carbon dioxide and oxygen was utilized to form microbubbles within alginate particles. Uniform alginate particles were obtained by a stable needle-based droplet formation process. Kinetic reaction of gas formation was monitored for 2% alginate particles. The gas formation increased with the concentrations of sodium bicarbonate (1-5 wt%) and hydrogen peroxide (0-36.5 wt%).

  17. A Facile Fabrication of Alginate Microbubbles Using a Gas Foaming Reaction

    Directory of Open Access Journals (Sweden)

    Chih-Hui Yang

    2013-08-01

    Full Text Available Microbubble particles have been extensively utilized as temporal templates for various biomedical applications. This study proposes a facile strategy to obtain microbubble-containing alginate particles (i.e., microbubbles inside alginate gel particles, called alginate microbubbles. The chemical reaction of sodium bicarbonate and hydrogen peroxide to produce gaseous carbon dioxide and oxygen was utilized to form microbubbles within alginate particles. Uniform alginate particles were obtained by a stable needle-based droplet formation process. Kinetic reaction of gas formation was monitored for 2% alginate particles. The gas formation increased with the concentrations of sodium bicarbonate (1–5 wt% and hydrogen peroxide (0–36.5 wt%.

  18. Nonlinear Imaging of Microbubble Contrast Agent Using the Volterra Filter: In Vivo Results.

    Science.gov (United States)

    Du, Juan; Liu, Dalong; Ebbini, Emad S

    2016-12-01

    A nonlinear filtering approach to imaging the dynamics of microbubble ultrasound contrast agents (UCAs) in microvessels is presented. The approach is based on the adaptive third-order Volterra filter (TVF), which separates the linear, quadratic, and cubic components from beamformed pulse-echo ultrasound data. The TVF captures polynomial nonlinearities utilizing the full spectral components of the echo data and not from prespecified bands, e.g., second or third harmonics. This allows for imaging using broadband pulse transmission to preserve the axial resolution and the SNR. In this paper, we present the results from imaging the UCA activity in a 200- [Formula: see text] cellulose tube embedded in a tissue-mimicking phantom using a linear array diagnostic probe. The contrast enhancement was quantified by computing the contrast-to-tissue ratio (CTR) for the different imaging components, i.e., B-mode, pulse inversion (PI), and the TVF components. The temporal mean and standard deviation of the CTR values were computed for all frames in a given data set. Quadratic and cubic images, referred to as QB-mode and CB-mode, produced higher mean CTR values than B-mode, which showed improved sensitivity. Compared with PI, they produced similar or higher mean CTR values with greater spatial specificity. We also report in vivo results from imaging UCA activity in an implanted LNCaP tumor with heterogeneous perfusion. The temporal means and standard deviations of the echogenicity were evaluated in small regions with different perfusion levels in the presence and absence of UCA. The in vivo measurements behaved consistently with the corresponding calculations obtained under microflow conditions in vitro. Specifically, the nonlinear VF components produced larger increases in the temporal mean and standard deviation values compared with B-mode in regions with low to relatively high perfusion. These results showed that polynomial filters such as the TVF can provide an important tool

  19. Quantifying and comparing dynamic predictive accuracy of joint models for longitudinal marker and time-to-event in presence of censoring and competing risks

    DEFF Research Database (Denmark)

    Blanche, Paul; Proust-Lima, Cécile; Loubère, Lucie

    2015-01-01

    's health profile grows with time. We focus in this work on statistical methods for quantifying and comparing dynamic predictive accuracy of this kind of prognostic models, accounting for right censoring and possibly competing events. Dynamic area under the ROC curve (AUC) and Brier Score (BS) are used......Thanks to the growing interest in personalized medicine, joint modeling of longitudinal marker and time-to-event data has recently started to be used to derive dynamic individual risk predictions. Individual predictions are called dynamic because they are updated when information on the subject...... psychometric tests to predict dementia in the elderly, accounting for the competing risk of death. Models are estimated on the French Paquid cohort and predictive accuracies are evaluated and compared on the French Three-City cohort....

  20. Efficient Sonochemistry through Microbubbles Generated with Micromachined Surfaces

    CERN Document Server

    Rivas, David Fernandez; Zijlstra, Aaldert G; Lohse, Detlef; Gardeniers, Han J G E; 10.1002/anie.201005533

    2012-01-01

    Sonochemical reactors are used in water treatment, the synthesis of fine chemicals, pharmaceutics and others. The low efficiency of sonoreactors have prevented its massive usage at industrial scales. Controlling the appearance of bubbles in place and time is the most limiting factor. A novel type of sonochemical reactor was designed making use of micro-fabrication techniques to control the nucleation sites of micro-bubbles. The efficiency was increased first by locating the nucleation sites in the most active region of a micro-chamber; additionally the desired chemical effect was significantly higher at the same powers than when not controlled. Silicon substrates were micromachined with "artificial nucleation sites" or pits, and placed at the bottom of the micro-chamber. The pits entrap gas which, upon ultrasonic excitation, sheds off a stream of microbubbles. The gas content of the pits is not depleted but is replenished by diffusion and the emission of microbubbles can continue for hours.

  1. Quasi-droplet Microbubbles for High Resolution Sensing Applications

    CERN Document Server

    Yang, Yong; Chormaic, Síle Nic

    2014-01-01

    Optical properties and sensing capabilities of fused silica microbubbles were studied numerically using a finite element method. Mode characteristics, such as quality factor (Q) and effective refractive index, were determined for different bubble diameters and shell thicknesses. For sensing applications with whispering gallery modes (WGMs), thinner shells yield improved sensitivity. However, the Q-factor decreases with reduced thickness and this limits the final resolution. Three types of sensing applications with microbubbles, based on their optimized geometrical parameters, were studied. Herein the so-called quasi-droplet regime is defined and discussed. It is shown that best resolution can be achieved when microbubbles act as quasi-droplets, even for water-filled cavities at the telecommunications C-band.

  2. Preparation of human hepatocellular carcinoma-targeted liposome microbubbles and their immunological properties

    Institute of Scientific and Technical Information of China (English)

    Ai-Na Bian; Yun-Hua Gao; Kai-Bin Tan; Ping Liu; Gong-Jun Zeng; Xin Zhang; Zheng Liu

    2004-01-01

    AIM: To prepare the human hepatocellular carcinoma.(HCC)-targeted liposome microbubbles and to investigate their immunological properties.METHODS: Human hepatocarcinoma specific monoclonal antibody HAb18 was attached to the surface of home-made liposome microbubbles by static attraction to prepare the targeted liposome microbubbles. The combination of HAb18 with liposome microbubbles was confirmed by the slide agglutination test and immunofluorescent assay. Their immunological activity was measured by ELISA. Rosette formation test, rosette formation blocking test and immunofluorescent assay were used to identify the specific binding of targeted liposome microbubbles to SMMC-7721 hepatoma cells, and cytotoxicity assay was used to detect their effect on human hepatocytes.RESULTS: The targeted liposome microbubbles were positive in the slide agglutination test and immunofluorescent assay. ELISA indicated that the immunological activity of HAb18 on the liposome microbubbles was similar to that of free HAb18. SMMC-7721 cells were surrounded by the targeting liposome microbubbles to form rosettes, while the control SGC-7901 gastric cancer cells were not. Proliferation of SMMC-7721 cells and normal human hepatocytes was not influenced by the targeted liposome microbubbles.CONCLUSION: The targeted liposome microbubbles with a high specific biological activity have been successfully prepared, which specifically bind to human hepatocarcinoma cells, and are non-cytotoxic to hepatocytes. These results indicate that the liposome microbubbles can be used as a HCC-targeted ultrasound contrast agent that may enhance ultrasound images and thus improve the diagnosis of HCC,especially at the early stage.

  3. Wideband Excitation of Microbubbles to Maximize the Sonoporation Efficiency and Contrast in Ultrasound Imaging

    CERN Document Server

    Harput, Sevan; Cowell, David M J; Freear, Steven

    2016-01-01

    The importance of the excitation bandwidth is well known in diagnostic ultrasound imaging. However, the effect of excitation bandwidth in therapeutic applications of microbubbles has been mostly overlooked. A majority of contrast agent production techniques generate polydisperse microbubble populations, so a wide range of resonance frequencies exist. Therefore, wideband excitation is necessary to fully utilize microbubble resonance behavior and maximize the reradiated energy from a microbubble population, both for imaging and therapy. Oscillations of sixty SonoVue microbubbles in proximity of a rigid boundary were captured on a high speed camera at 3 Mfps, excited with a peak negative pressure of 50 kPa at 1 MHz. Measurements were analyzed according to their peak radiated pressure, radial oscillations, root mean squared pressure, and shear stress generated by microbubbles. Results showed that long duration and wideband excitation at low intensity levels was preferable for sonoporation, where microbubbles can ...

  4. Robust Microbubble Tracking for Super Resolution Imaging in Ultrasound

    DEFF Research Database (Denmark)

    Hansen, kristoffer B; Villagómez-Hoyos, Carlos A; Brasen, Jens Christian

    2016-01-01

    Currently ultrasound resolution is limited by diffraction to approximately half the wavelength of the sound wave employed. In recent years, super resolution imaging techniques have overcome the diffraction limit through the localization and tracking of a sparse set of microbubbles through...... the vasculature. However, this has only been performed on fixated tissue, limiting its clinical application. This paper proposes a technique for making super resolution images on non-fixated tissue by first compensating for tissue movement and then tracking the individual microbubbles. The experiment is performed...

  5. Permeability dependence study of the focused ultrasound-induced blood-brain barrier opening at distinct pressures and microbubble diameters using DCE-MRI.

    Science.gov (United States)

    Vlachos, Fotios; Tung, Yao-Sheng; Konofagou, Elisa

    2011-09-01

    Blood-brain barrier opening using focused ultrasound and microbubbles has been experimentally established as a noninvasive and localized brain drug delivery technique. In this study, the permeability of the opening is assessed in the murine hippocampus after the application of focused ultrasound at three different acoustic pressures and microbubble sizes. Using dynamic contrast-enhanced MRI, the transfer rates were estimated, yielding permeability maps and quantitative K(trans) values for a predefined region of interest. The volume of blood-brain barrier opening according to the K(trans) maps was proportional to both the pressure and the microbubble diameter. A K(trans) plateau of ∼0.05 min(-1) was reached at higher pressures (0.45 and 0.60 MPa) for the larger sized bubbles (4-5 and 6-8 μm), which was on the same order as the K(trans) of the epicranial muscle (no barrier). Smaller bubbles (1-2 μm) yielded significantly lower permeability values. A small percentage (7.5%) of mice showed signs of damage under histological examination, but no correlation with permeability was established. The assessment of the blood-brain barrier permeability properties and their dependence on both the pressure and the microbubble diameter suggests that K(trans) maps may constitute an in vivo tool for the quantification of the efficacy of the focused ultrasound-induced blood-brain barrier opening.

  6. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging

    Directory of Open Access Journals (Sweden)

    Vivian M. Hsu, MD

    2014-09-01

    Conclusions: This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.

  7. Numerical study on the effective heating due to inertial cavitation in microbubble-enhanced HIFU therapy

    Science.gov (United States)

    Okita, Kohei; Sugiyama, Kazuyasu; Takagi, Shu; Matsumoto, Yoichiro

    2015-10-01

    The enhancement of heating due to inertial cavitation was focused in high-intensity focused ultrasound (HIFU) therapy. The influences of the rectified diffusion on microbubble-enhanced HIFU were examined numerically. A bubble dynamics equation in consideration of the spherical shell bubble and the elasticity of surrounding tissue was employed. Mass and heat transfer between the surrounding medium and the bubble were considered. The basic equations were discretized by finite difference method. The mixture phase and bubbles are coupled by the Euler-Lagrange method to take into account the interaction between ultrasound and bubbles. The mass transfer rate of gas from the surrounding medium to the bubble was examined as function of the initial bubble radius and the driving pressure amplitude. As the results, the pressure required to bubble growth was decreases with increasing the initial bubble radius. Thus, the injection of microbubble reduces the cavitation threshold pressure. On the other hand, the influence of the rectified diffusion on the triggered HIFU therapy which generates cavitation bubbles by high-intensity burst and induces the localized heating owing to cavitation bubble oscillation by low-intensity continuous waves. The calculation showed that the localized heating was enhanced by the increase of the equilibrium bubble size due to the rectified diffusion.

  8. Nonlinear oscillation and interfacial stability of an encapsulated microbubble under dual-frequency ultrasound

    Science.gov (United States)

    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.

  9. Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening

    Science.gov (United States)

    Wu, Sheng-Kai; Chu, Po-Chun; Chai, Wen-Yen; Kang, Shih-Tsung; Tsai, Chih-Hung; Fan, Ching-Hsiang; Yeh, Chih-Kuang; Liu, Hao-Li

    2017-04-01

    Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as surrogates to allow molecule-penetrated quantification, BBB-opened observation, and MBs circulation/persistence. Cavitation activity was measured via the passive cavitation detection (PCD) setup to correlate with the exposure level and the histological effect. Under given and identical MB concentrations, the three MBs induced similar and equivalent BBB-opening effects and persistence. In addition, a treatment paradigm by adapting exposure time is proposed to compensate MB decay to retain the persistence of BBB-opening efficiency in multiple FUS exposures. The results potentially improve understanding of the equivalence among MBs in focused ultrasound CNS drug delivery, and provide an effective strategy for securing persistence in this treatment modality.

  10. Correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size

    Directory of Open Access Journals (Sweden)

    Chenshi ZHANG

    2008-02-01

    Full Text Available Background and Objective The solitary pulmonary nodules (SPNs is one of the most common findings on chest radiographs. It becomes possible to provide more accurately quantitative information about blood flow patterns of solitary pulmonary nodules (SPNs with multi-slice spiral computed tomography (MSCT. The aim of this study is to evaluate the correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size. Methods 68 patients with maliagnant solitary pulmonary nodules (SPNs (diameter <=4 cmunderwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4mL/s by an autoinjector, 4*5mm or 4*2.5mm scanning mode with stable table were performed. serial CT. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion (PSPN, peak height (PHSPNratio of peak height of the SPN to that of the aorta (SPN-to-A ratioand mean transit time(MTT were calculated. The correlation between the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules and tumor size were assessed by means of linear regression analysis. Results No significant correlations were found between the tumor size and each of the peak height (PHSPN ratio of peak height of the SPN to that of the aorta (SPN-to-A ratio perfusion(PSPNand mean transit time (r=0.18, P=0.14; r=0.20,P=0.09; r=0.01, P=0.95; r=0.01, P=0.93. Conclusion No significant correlation is found between the tumor size and each of the quantifiable parameters of blood flow pattern derived with dynamic CT in maliagnant solitary pulmonary nodules.

  11. Microbubble-enriched lavage fluid for treatment of experimental peritonitis

    NARCIS (Netherlands)

    Sharma, P. K.; Rakhorst, G.; Engels, E.; van der Mei, H. C.; Busscher, H. J.; Ploeg, R. J.

    2008-01-01

    Background: Relaparotomies and closed postoperative peritoneal lavage (CPPL) are performed to treat persistent peritonitis. This experimental animal study compared open abdominal lavage with CPPL, and evaluated the potential of microbubble-enriched lavage fluids to improve the efficiency of CPPL and

  12. On the Near Surface Population of Oceanic Microbubbles

    Science.gov (United States)

    1989-06-01

    and J = 5. The slope of Monahan’s curves indic acs an r-4-3 dependance , approximately. During a number of the experimental runs of Walsh and...O’Muircheartaigh, I.G. Coverage Dependance on Wind-Speed". J. Phys. Oceanogr., 10, pp.2094-2099, 1980 8 Tate, P.M. "The Distribution of Ocean Microbubbles

  13. Micromanipulation of endothelial cells: Ultrasound-microbubble-cell interaction

    NARCIS (Netherlands)

    Wamel, van Annemieke; Bouakaz, Ayache; Versluis, Michel; Jong, de Nico

    2004-01-01

    Ultrasound (US) in combination with contrast microbubbles has been shown to alter the permeability of cell membranes without affecting cell viability. This permeabilisation feature is used to design new drug delivery systems using US and contrast agents. The underlying mechanisms are still unknown.

  14. Biological in situ characterization of polymeric microbubble contrast agents

    NARCIS (Netherlands)

    Wan, Sha; Egri, Gabriella; Oddo, Letizia; Cerroni, Barbara; Dähne, Lars; Paradossi, Gaio; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A; Monopoli, Marco P

    2016-01-01

    Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging.

  15. Acoustic characterization of single ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

    Sijl, Jeroen; Gaud, Emmanuel; Frinking, Peter J.A.; Arditi, Marcel; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2008-01-01

    Individual ultrasound contrast agent microbubbles (BR14) were characterized acoustically. The bubbles were excited at a frequency of 2 MHz and at peak-negative pressure amplitudes of 60 and 100 kPa. By measuring the transmit and receive transfer functions of both the transmit and receive transduce

  16. The acoustics of diagnostic microbubbles: dissipative effects and heat deposition

    NARCIS (Netherlands)

    Hilgenfeldt, Sascha; Lohse, Detlef

    2000-01-01

    We discuss the effectively detectable scattered intensity of ultrasound from diagnostic microbubble suspensions, taking dissipative mechanisms in the liquid medium into account. In particular, we conclude that neither non-linear wave steepening of the incident (driving) wave nor of the outgoing (sca

  17. Acoustic behavior of microbubbles and implications for drug delivery

    NARCIS (Netherlands)

    Kooiman, K.; Vos, H.J.; Versluis, M.; Jong, de N.

    2014-01-01

    Ultrasound contrast agents are valuable in diagnostic ultrasound imaging, and they increasingly show potential for drug delivery. This review focuses on the acoustic behavior of flexible-coated microbubbles and rigid-coated microcapsules and their contribution to enhanced drug delivery. Phenomena re

  18. Subharmonic response of encapsulated microbubbles: conditions for existence and amplification.

    Science.gov (United States)

    Kimmel, Eitan; Krasovitski, Boris; Hoogi, Assaf; Razansky, Daniel; Adam, Dan

    2007-11-01

    The response of encapsulated microbubbles at half the ultrasound insonation frequency, termed subharmonic response, may have potential applications in diagnosis and therapy. The subharmonic signal, emitted by Definity microbubble cloud sonicated by ultrasound was studied theoretically and experimentally. The size distribution of the microbubbles was optically analyzed and resonance frequency of 2.7 MHz was determined. An asymptotic model has been developed that generates subharmonic response of a single and of a cloud of bubbles of various sizes. Threshold conditions for existence and the intensity of the subharmonic signal are predicted to depend on microbubbles size distribution and shell properties, as well as on the driving field frequency and pressure. Thin tubes filled with Definity solution were insonated at acoustic pressures from 100 to 630 kPa. The intensities of the emitted fundamental harmonics and subharmonics were measured. At frequency 5.5MHz, twice the resonance frequency, the subharmonic signals were observed only at pressures greater than 190 kPa. The subharmonic to fundamental harmonics intensity ratio was within -12 to -1 dB. The experimental results showed good correlation with the theoretical results in the range of validity of the asymptotic solution, thus supporting the model assumptions.

  19. Microbubble Swarms in a Full-Scale Water Model Tundish

    Science.gov (United States)

    Chang, Sheng; Cao, Xiangkun; Zou, Zongshu; Isac, Mihaiela; Guthrie, Roderick I. L.

    2016-10-01

    Water modeling, using microbubble swarms, was performed in a full-scale, four-strand, delta-shaped tundish, located at the McGill Metals Processing Centre (MMPC). The objective of the study was to investigate the effectiveness of microbubbles in removing inclusions smaller than 50 μm, applying the principles and conditions previously researched using a smaller scale arrangement. Air was injected into a full-scale model of a ladle shroud (the connecting tube through which liquid steel flows into the tundish below). The model ladle shroud was fitted with twelve, laser-drilled orifices, so as to create microbubbles. The bubbles generated using different gas injection protocols were recorded using a high-speed camera, and the bubble images were postprocessed using the commercial software, ImageJ. With this newly designed ladle shroud, bubble sizes could be reduced dramatically, to as small as a 675 µm average diameter. A three-dimensional, CFD model simulation was developed, using parameters obtained from the corresponding water model experiments, in order to predict the behavior of these microbubbles within the tundish and their potential influence on flow patterns and inclusion float-out capability.

  20. Real-Time Two-Dimensional Imaging of Microbubble Cavitation

    NARCIS (Netherlands)

    Vignon, F.; Shi, W.T.; Powers, J.E.; Liu, J.; Drvol, L.; Lof, J.; Everbach, C.; Gao, S.; Xie, F.; Porter, T.

    2011-01-01

    Ultrasound cavitation of microbubble contrast agents has a potentialfor therapeutic applications, including sonothrombolysis in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (e.g. stable versus inertial forms of cavitat

  1. [Characteristics of acid red 3R wastewater treatment by ozone microbubbles].

    Science.gov (United States)

    Zhang, Jing; Du, Ya-Wei; Liu, Xiao-Jing; Zhou, Yu-Wen; Liu, Chun; Yang, Jing-Liang; Zhang, Lei

    2015-02-01

    The application of microbubble technology for ozonation wastewater treatment could enhance ozone mass transfer, improve ozonation performance and increase ozone utilization efficiency. The ozone microbubbles were used to treat synthetic acid red 3R wastewater in the present study, and compared to ozone conventional bubbles. The ozone mass transfer and ozonation characteristics of acid red 3R were investigated when ozone microbubbles and ozone conventional bubbles were applied. The results confirmed the enhanced ozone mass transfer using microbubbles. The ozone mass transfer coefficient using microbubbles was 3.6 times higher than that using conventional bubbles under the same conditions. Simultaneously, the ozone decomposition coefficient using microbubbles was 6.2 times higher than that using conventional bubbles, which would be favorable for *OH generation. The ozonation rate and mineralization efficiency of acid red 3R could be improved significantly using ozone microbubbles. A TOC removal efficiency of 78.0% was achieved using ozone microbubbles, which was about 2 times higher than that using ozone conventional bubbles. The ozone utilization efficiency using microbubbles was much higher that using conventional bubbles during ozonation treatment of acid red 3R. The average ozone utilization efficiencies were 97.8% and 69.3% when microbubbles and conventional bubbles were used, respectively. The oxidative ability of ozone microbubbles could be increased by enhancing *OH generation, and as a result, the oxidative reaction of degradation intermediates was accelerated by ozone microbubbles. Especially, the mineralization ability of small organic acid intermediates using ozone microbubbles was about 1.6 times higher than that using ozone conventional bubbles.

  2. Microbubbles shunting via a patent foramen ovale impair endothelial function

    Directory of Open Access Journals (Sweden)

    Henry Fok

    2015-08-01

    Full Text Available Objectives Exposure to intravascular microbubbles after diving and during medical procedures alters endothelial function. The aim of this study was to investigate whether a patent foramen ovale altered forearm endothelial function by facilitating microbubbles transfer. Design Patients attended on two separate visits, at least seven days apart receiving agitated saline or no active intervention in random order. On both days, flow-mediated dilatation of the brachial artery was measured using vascular ultrasound. On the intervention visit, agitated saline was injected and the passage of microbubbles into the arterial circulation was confirmed by echocardiography. Serial flow-mediated dilatation measurements were made after agitated saline and at the same time points after no intervention. Setting St Thomas’ Hospital in London. Participants Patients with a patent foramen ovale (PFO+n = 14, 9 male, mean ± SD age 42.2 ± 10.5 years and patients without a patent foramen ovale (PFO− n = 10, 7 male, mean ± SD age 49.4 ± 18.4 years were recruited. Main outcome measures Change in brachial artery flow-mediated dilatation. Results In patent foramen ovale + patients, flow-mediated dilatation did not change significantly on the control day but after agitated saline reduced by 2.3 ± 0.3%, 20 minutes after bubble injection (P < 0.005 vs. corresponding change in flow-mediated dilatation during control study. There was no significant change in flow-mediated dilatation for patent foramen ovale− patients at either visit. Conclusion These results suggest that the presence of a patent foramen ovale facilitated impairment of endothelial function acutely by the transfer of microbubbles into the arterial circulation. As a patent foramen ovale is a common condition, this may be relevant to microbubbles exposure in medical procedures and in decompression illness.

  3. Quantifying the Impacts of Environmental Factors on Vegetation Dynamics over Climatic and Management Gradients of Central Asia

    Directory of Open Access Journals (Sweden)

    Olena Dubovyk

    2016-07-01

    Full Text Available Currently there is a lack of quantitative information regarding the driving factors of vegetation dynamics in post-Soviet Central Asia. Insufficient knowledge also exists concerning vegetation variability across sub-humid to arid climatic gradients as well as vegetation response to different land uses, from natural rangelands to intensively irrigated croplands. In this study, we analyzed the environmental drivers of vegetation dynamics in five Central Asian countries by coupling key vegetation parameter “overall greenness” derived from Moderate Resolution Imaging Spectroradiometer (MODIS Normalized Difference Vegetation Index (NDVI time series data, with its possible factors across various management and climatic gradients. We developed nine generalized least-squares random effect (GLS-RE models to analyze the relative impact of environmental factors on vegetation dynamics. The obtained results quantitatively indicated the extensive control of climatic factors on managed and unmanaged vegetation cover across Central Asia. The most diverse vegetation dynamics response to climatic variables was observed for “intensively managed irrigated croplands”. Almost no differences in response to these variables were detected for managed non-irrigated vegetation and unmanaged (natural vegetation across all countries. Natural vegetation and rainfed non-irrigated crop dynamics were principally associated with temperature and precipitation parameters. Variables related to temperature had the greatest relative effect on irrigated croplands and on vegetation cover within the mountainous zone. Further research should focus on incorporating the socio-economic factors discussed here in a similar analysis.

  4. Quantifying the potential of automated dynamic solar shading in office buildings through integrated simulations of energy and daylight

    DEFF Research Database (Denmark)

    Nielsen, Martin Vraa; Svendsen, Svend; Bjerregaard Jensen, Lotte

    2011-01-01

    The façade design is and should be considered a central issue in the design of energy-efficient buildings. That is why dynamic façade components are increasingly used to adapt to both internal and external impacts, and to cope with a reduction in energy consumption and an increase in occupant com...... solar shading, which emphasises the need for dynamic and integrated simulations early in the design process to facilitate informed design decisions about the façade....... components by using integrated simulations that took energy demand, the indoor air quality, the amount of daylight available, and visual comfort into consideration. Three types of façades were investigated (without solar shading, with fixed solar shading, and with dynamic solar shading), and we simulated...

  5. Locomotor forces on a swimming fish: three-dimensional vortex wake dynamics quantified using digital particle image velocimetry.

    Science.gov (United States)

    Drucker; Lauder

    1999-01-01

    Quantifying the locomotor forces experienced by swimming fishes represents a significant challenge because direct measurements of force applied to the aquatic medium are not feasible. However, using the technique of digital particle image velocimetry (DPIV), it is possible to quantify the effect of fish fins on water movement and hence to estimate momentum transfer from the animal to the fluid. We used DPIV to visualize water flow in the wake of the pectoral fins of bluegill sunfish (Lepomis macrochirus) swimming at speeds of 0.5-1.5 L s(-)(1), where L is total body length. Velocity fields quantified in three perpendicular planes in the wake of the fins allowed three-dimensional reconstruction of downstream vortex structures. At low swimming speed (0.5 L s(-)(1)), vorticity is shed by each fin during the downstroke and stroke reversal to generate discrete, roughly symmetrical, vortex rings of near-uniform circulation with a central jet of high-velocity flow. At and above the maximum sustainable labriform swimming speed of 1.0 L s(-)(1), additional vorticity appears on the upstroke, indicating the production of linked pairs of rings by each fin. Fluid velocity measured in the vicinity of the fin indicates that substantial spanwise flow during the downstroke may occur as vortex rings are formed. The forces exerted by the fins on the water in three dimensions were calculated from vortex ring orientation and momentum. Mean wake-derived thrust (11.1 mN) and lift (3.2 mN) forces produced by both fins per stride at 0.5 L s(-)(1) were found to match closely empirically determined counter-forces of body drag and weight. Medially directed reaction forces were unexpectedly large, averaging 125 % of the thrust force for each fin. Such large inward forces and a deep body that isolates left- and right-side vortex rings are predicted to aid maneuverability. The observed force balance indicates that DPIV can be used to measure accurately large-scale vorticity in the wake of

  6. Tunable erbium-doped microbubble laser fabricated by sol-gel coating

    CERN Document Server

    Yang, Yong; Kasumie, Sho; Xu, Linhua; Ward, Jonathan; Yang, Lan; Chormaic, Síle Nic

    2016-01-01

    In this work, we show that the application of a sol-gel coating renders a microbubble whispering gallery resonator into an active device. During the fabrication of the resonator, a thin layer of erbium-doped sol-gel is applied to a tapered microcapillary, then a microbubble with a wall thickness of 1.3 $\\mu$m is formed with the rare earth diffused into its walls. The doped microbubble is pumped at 980 nm and lasing in the emission band of the Er$^{3+}$ ions with a wavelength of 1535 nm is observed. The laser wavelength can be tuned by aerostatic pressure tuning of the whispering gallery modes of the microbubble. Up to 240 pm tuning is observed with 2 bar of applied pressure. It is shown that the doped microbubble could be used as a compact, tunable laser source. The lasing microbubble can also be used to improve sensing capabilities in optofluidic sensing applications.

  7. Optimal design and experimental measurement of the subharmonic characterizations of encapsulated microbubble

    Institute of Scientific and Technical Information of China (English)

    ZONG Yujin; WAN Mingxi; WANG Suping; CHEN Hong; ZHANG Guolu

    2006-01-01

    Based on a theoretical motion equation of encapsulated microbubbles within an ultrasound field, the subharmonic characterizations of microbubbles are optimally designed and analyzed by a computer aided design system. The effects of size, shell elasticity and acoustic pressure on subharmonic response of microbubbles are calculated theoretically to obtain the optimal parameters for nondestructive subharmonic imaging. In addition, microbubbles with different shell elasticity are prepared, and their subharmonic responses are measured in vitro.The results of theoretical calculation and acoustic measurement show that good subharmonic enhancement can be obtained by using the encapsulated microbubbles with the mean size of 3μm, which were prepared from the surfactant solution with the proper ratio of shell material.It is also shown that the best operating acoustic pressure is 200 to 400 kPa for nondestructive subharmonic imaging based on such kind of microbubbles.

  8. Quantifying the dynamics of flow within a permeable bed using time-resolved endoscopic particle imaging velocimetry (EPIV)

    Energy Technology Data Exchange (ETDEWEB)

    Blois, G. [University of Birmingham, School of Geography, Earth and Environmental Sciences, Birmingham (United Kingdom); University of Illinois, Department of Mechanical Science and Engineering, Urbana, IL (United States); Sambrook Smith, G.H.; Lead, J.R. [University of Birmingham, School of Geography, Earth and Environmental Sciences, Birmingham (United Kingdom); Best, J.L. [University of Illinois, Departments of Geology, Geography, Mechanical Science and Engineering, and Ven Te Chow Hydrosystems Laboratory, Urbana, IL (United States); Hardy, R.J. [Durham University, Department of Geography, Science Laboratories, Durham (United Kingdom)

    2012-07-15

    This paper presents results of an experimental study investigating the mean and temporal evolution of flow within the pore space of a packed bed overlain by a free-surface flow. Data were collected by an endoscopic PIV (EPIV) technique. EPIV allows the instantaneous velocity field within the pore space to be quantified at a high spatio-temporal resolution, thus permitting investigation of the structure of turbulent subsurface flow produced by a high Reynolds number freestream flow (Re{sub s} in the range 9.8 x 10{sup 3}-9.7 x 10{sup 4}). Evolution of coherent flow structures within the pore space is shown to be driven by jet flow, with the interaction of this jet with the pore flow generating distinct coherent flow structures. The effects of freestream water depth, Reynolds and Froude numbers are investigated. (orig.)

  9. Small amplitude Dynamic AFM: quantifying interactions with different tip detection and excitation schemes in presence of additional resonances

    CERN Document Server

    Costa, Luca

    2014-01-01

    Quantifying the tip-sample interaction at the nanoscale in Amplitude Modulation mode AFM is challenging, especially when measuring in liquids. Here, we derive formulas for the tip-sample conservative and dissipative interactions and investigate the effect that spurious resonances have on the measured interaction. Both direct and acoustic excitation are considered. We also highlight the differences between measuring directly the tip position or the cantilever deflection. We show that, when probing the tip-sample forces, the acoustically excited cantilever behavior is insensitive to spurious resonances as long as the measured signal corresponds to the tip position, or if the excitation force is correctly taken into account. Since the effective excitation force may depend on the presence of such spurious resonances, we consider the cases where the frequency is kept constant during the measurement so that the proportionality between excitation signal and actual excitation force is kept constant. With the present ...

  10. Quantifying the patterns and dynamics of river deltas under conditions of steady forcing and relative sea level rise

    Science.gov (United States)

    Liang, Man; Van Dyk, Corey; Passalacqua, Paola

    2016-02-01

    Understanding deltaic channel dynamics is essential to acquiring knowledge on how deltas respond to environmental changes, as channels control the distribution of water, sediment, and nutrients. Channel-resolving morphodynamic models provide the basis for quantitative study of channel-scale dynamics, but they need to be properly assessed with a set of robust metrics able to quantitatively characterize delta patterns and dynamics before being used as predictive tools. In this work we use metrics developed in the context of delta formation, to assess the morphodynamic results of DeltaRCM, a parcel-based cellular model for delta formation and evolution. By comparing model results to theoretical predictions and field and experimental observations, we show that DeltaRCM captures the geometric growth characteristics of deltas such as fractality of channel network, spatial distribution of wet and dry surfaces, and temporal dynamics of channel-scale processes such as the decay of channel planform correlation. After evaluating the ability of DeltaRCM to produce delta patterns and dynamics at the scale of channel processes, we use the model to predict the deltaic response to relative sea level rise (RSLR). We show that uniform subsidence and absolute sea level rise have similar effects on delta evolution and cause intensified channel branching. Channel network fractality and channel mobility increase with higher-RSLR rates, while the spatial and temporal scales of avulsion events decrease, resulting in smaller sand bodies in the stratigraphy. Our modeling results provide the first set of quantitative predictions of the effects of RSLR on river deltas with a specific focus on the distributary channel network.

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

    OpenAIRE

    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 effecti...

  12. Ultrasound in Biomedical Engineering: Ultrasound Microbubble Contrast Agents Promote Transdermal Permeation of Drugs

    Directory of Open Access Journals (Sweden)

    Ai-Ho Liao

    2016-09-01

    Full Text Available This report discusses a new development in the use of ultrasound microbubble contrast agents on transdermal drug delivery. The medium surrounding the microbubbles at the optimum concentration from liquid to gel can be modified and it can still achieve the same enhancement for transdermal drug permeation as liquid medium. It was also found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface.

  13. Two porous luminescent metal-organic frameworks: quantifiable evaluation of dynamic and static luminescent sensing mechanisms towards Fe(3.).

    Science.gov (United States)

    Jin, Jun-Cheng; Pang, Ling-Yan; Yang, Guo-Ping; Hou, Lei; Wang, Yao-Yu

    2015-10-21

    Two novel porous luminescent metal-organic frameworks (MOFs, 1 and 2) have been constructed using 3,4-di(3,5-dicarboxyphenyl)phthalic acid using a hydrothermal method. Both MOFs can work as highly sensitive sensors to Fe(3+) by luminescent quenching. Analyses of the structures indicate a higher quenching efficiency of 2 because of the existence of active -COOH groups. Based on this consideration, the quenching mechanisms are studied and the processes are controlled by multiple mechanisms in which dynamic and static mechanisms of MOFs are discussed. Besides, the corresponding dynamic and static quenching constants are calculated, achieving the quantification evaluation of the quenching process. As expected, experimental data show that compound 2 possesses an overall quenching efficiency 6.9 times that of compound 1. Additionally, time-dependent intensity measurements, the shifts of the excitation spectrum and the appearance of a new emission peak all give visual proofs of the distinct mechanisms between the two MOFs.

  14. Development and application of methods to quantify spatial and temporal hyperpolarized 3He MRI ventilation dynamics: preliminary results in chronic obstructive pulmonary disease

    Science.gov (United States)

    Kirby, Miranda; Wheatley, Andrew; McCormack, David G.; Parraga, Grace

    2010-03-01

    Hyperpolarized helium-3 (3He) magnetic resonance imaging (MRI) has emerged as a non-invasive research method for quantifying lung structural and functional changes, enabling direct visualization in vivo at high spatial and temporal resolution. Here we described the development of methods for quantifying ventilation dynamics in response to salbutamol in Chronic Obstructive Pulmonary Disease (COPD). Whole body 3.0 Tesla Excite 12.0 MRI system was used to obtain multi-slice coronal images acquired immediately after subjects inhaled hyperpolarized 3He gas. Ventilated volume (VV), ventilation defect volume (VDV) and thoracic cavity volume (TCV) were recorded following segmentation of 3He and 1H images respectively, and used to calculate percent ventilated volume (PVV) and ventilation defect percent (VDP). Manual segmentation and Otsu thresholding were significantly correlated for VV (r=.82, p=.001), VDV (r=.87 p=.0002), PVV (r=.85, p=.0005), and VDP (r=.85, p=.0005). The level of agreement between these segmentation methods was also evaluated using Bland-Altman analysis and this showed that manual segmentation was consistently higher for VV (Mean=.22 L, SD=.05) and consistently lower for VDV (Mean=-.13, SD=.05) measurements than Otsu thresholding. To automate the quantification of newly ventilated pixels (NVp) post-bronchodilator, we used translation, rotation, and scaling transformations to register pre-and post-salbutamol images. There was a significant correlation between NVp and VDV (r=-.94 p=.005) and between percent newly ventilated pixels (PNVp) and VDP (r=- .89, p=.02), but not for VV or PVV. Evaluation of 3He MRI ventilation dynamics using Otsu thresholding and landmark-based image registration provides a way to regionally quantify functional changes in COPD subjects after treatment with beta-agonist bronchodilators, a common COPD and asthma therapy.

  15. Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy.

    Science.gov (United States)

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

    2012-12-01

    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 EGF receptor (EGFR)-directed 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 time, 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.

  16. Ultrasound/Microbubble Enhances Foreign Gene Expression in ECV304 Cells and Murine Myocardium

    Institute of Scientific and Technical Information of China (English)

    Dongping GUO; Xiaorong LI; Xiaoyu LI; Ping SUN; Zhiguang WANG; Xiuying CHEN; Qi CHEN; Leming FAN; Bin ZHANG; Lizheng SHAO

    2004-01-01

    Although viral vectors are efficient systems to transfer foreign genes into cells or target tissues,safety issues remain in relation to human gene therapy. Microbubbles currently used as ultrasound contrast agents have been applied in transfection of genes. This study was designed to test the transfection efficiency and the expression of exogenous gene mediated by ultrasound irradiation enhanced air filled albumin microbubbles in ECV304 cell line in vitro and the heart of the mouse in vivo. Air filled microbubbles (2.0-4.0 μm in diameter) were created by sonicating the mixture of human albumin, glucose, mannitol and special additive that was designed for stabilization. Plasmid DNA loading the reporter genes was gently mixed with microbubbles. The mixture of plasmid DNA and microbubbles was administrated to cultured ECV304 cells and BALB/c mice (tail vein injection) under different ultrasound/microbubble conditions, and then the transfection and expression efficiency were examined. The results both in vivo and in vitro demonstrated that microbubble with ultrasound irradiation could significantly elevate the exogenous gene expression as compared with microbubble or ultrasound only. Overall, the present study showed that the ultrasound-target microbubble destruction method enhanced the exogenous gene expression in vivo and in vitro, and provided a gene therapy way not only efficient but also easy to be manipulated and carried out in clinical.

  17. Coupling of drug containing liposomes to microbubbles improves ultrasound triggered drug delivery in mice.

    Science.gov (United States)

    Cool, Steven K; Geers, Bart; Roels, Stefan; Stremersch, Stephan; Vanderperren, Katrien; Saunders, Jimmy H; De Smedt, Stefaan C; Demeester, Joseph; Sanders, Niek N

    2013-12-28

    Local extravasation and triggered drug delivery by use of ultrasound and microbubbles is a promising strategy to target drugs to their sites of action. In the past we have developed drug loaded microbubbles by coupling drug containing liposomes to the surface of microbubbles. Until now the advantages of this drug loading strategy have only been demonstrated in vitro. Therefore, in this paper, microbubbles with indocyanine green (ICG) containing liposomes at their surface or a mixture of ICG-liposomes and microbubbles was injected intravenously in mice. Immediately after injection the left hind leg was exposed to 1 MHz ultrasound and the ICG deposition was monitored 1, 4 and 7 days post-treatment by in vivo fluorescence imaging. In mice that received the ICG-liposome loaded microbubbles the local ICG deposition was, at each time point, about 2-fold higher than in mice that received ICG-liposomes mixed with microbubbles. We also showed that the perforations in the blood vessels allow the passage of ICG-liposomes up to 5h after microbubble and ultrasound treatment. An increase in tissue temperature to 41°C was observed in all ultrasound treated mice. However, ultrasound tissue heating was excluded to cause the local ICG deposition. We concluded that coupling of drug containing liposomes to microbubbles may increase ultrasound mediated drug delivery in vivo.

  18. A model for an acoustically driven microbubble inside a rigid tube

    KAUST Repository

    Qamar, Adnan

    2014-09-10

    A theoretical framework to model the dynamics of acoustically driven microbubble inside a rigid tube is presented. The proposed model is not a variant of the conventional Rayleigh-Plesset category of models. It is derived from the reduced Navier-Stokes equation and is coupled with the evolving flow field solution inside the tube by a similarity transformation approach. The results are computed, and compared with experiments available in literature, for the initial bubble radius of Ro=1.5μm and 2μm for the tube diameter of D=12μm and 200μm with the acoustic parameters as utilized in the experiments. Results compare quite well with the existing experimental data. When compared to our earlier basic model, better agreement on a larger tube diameter is obtained with the proposed coupled model. The model also predicts, accurately, bubble fragmentation in terms of acoustic and geometric parameters.

  19. Nonlinear response of ultrasound contrast agent microbubbles: From fundamentals to applications

    Science.gov (United States)

    Teng, Xu-Dong; Guo, Xia-Sheng; Tu, Juan; Zhang, Dong

    2016-12-01

    Modelling and biomedical applications of ultrasound contrast agent (UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including (i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry; (ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size; (iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and (iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures. Projects supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 11374155, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the National High-Technology Research and Development Program, China (Grant No. 2012AA022702), and Qing Lan Project of Jiangsu Province, China.

  20. Quantifying variation in forest disturbance, and its effects on aboveground biomass dynamics, across the eastern United States.

    Science.gov (United States)

    Vanderwel, Mark C; Coomes, David A; Purves, Drew W

    2013-05-01

    The role of tree mortality in the global carbon balance is complicated by strong spatial and temporal heterogeneity that arises from the stochastic nature of carbon loss through disturbance. Characterizing spatio-temporal variation in mortality (including disturbance) and its effects on forest and carbon dynamics is thus essential to understanding the current global forest carbon sink, and to predicting how it will change in future. We analyzed forest inventory data from the eastern United States to estimate plot-level variation in mortality (relative to a long-term background rate for individual trees) for nine distinct forest regions. Disturbances that produced at least a fourfold increase in tree mortality over an approximately 5 year interval were observed in 1-5% of plots in each forest region. The frequency of disturbance was lowest in the northeast, and increased southwards along the Atlantic and Gulf coasts as fire and hurricane disturbances became progressively more common. Across the central and northern parts of the region, natural disturbances appeared to reflect a diffuse combination of wind, insects, disease, and ice storms. By linking estimated covariation in tree growth and mortality over time with a data-constrained forest dynamics model, we simulated the implications of stochastic variation in mortality for long-term aboveground biomass changes across the eastern United States. A geographic gradient in disturbance frequency induced notable differences in biomass dynamics between the least- and most-disturbed regions, with variation in mortality causing the latter to undergo considerably stronger fluctuations in aboveground stand biomass over time. Moreover, regional simulations showed that a given long-term increase in mean mortality rates would support greater aboveground biomass when expressed through disturbance effects compared with background mortality, particularly for early-successional species. The effects of increased tree mortality on

  1. Annual dynamics of daylight variability and contrast a simulation-based approach to quantifying visual effects in architecture

    CERN Document Server

    Rockcastle, Siobhan

    2013-01-01

    Daylight is a dynamic source of illumination in architectural space, creating diverse and ephemeral configurations of light and shadow within the built environment. Perceptual qualities of daylight, such as contrast and temporal variability, are essential to our understanding of both material and visual effects in architecture. Although spatial contrast and light variability are fundamental to the visual experience of architecture, architects still rely primarily on intuition to evaluate their designs because there are few metrics that address these factors. Through an analysis of contemporary

  2. Quantifying Concordance

    CERN Document Server

    Seehars, Sebastian; Amara, Adam; Refregier, Alexandre

    2015-01-01

    Quantifying the concordance between different cosmological experiments is important for testing the validity of theoretical models and systematics in the observations. In earlier work, we thus proposed the Surprise, a concordance measure derived from the relative entropy between posterior distributions. We revisit the properties of the Surprise and describe how it provides a general, versatile, and robust measure for the agreement between datasets. We also compare it to other measures of concordance that have been proposed for cosmology. As an application, we extend our earlier analysis and use the Surprise to quantify the agreement between WMAP 9, Planck 13 and Planck 15 constraints on the $\\Lambda$CDM model. Using a principle component analysis in parameter space, we find that the large Surprise between WMAP 9 and Planck 13 (S = 17.6 bits, implying a deviation from consistency at 99.8% confidence) is due to a shift along a direction that is dominated by the amplitude of the power spectrum. The Surprise disa...

  3. Comparing encapsulation efficiency and ultrasound-triggered release for protein between phospholipid-based microbubbles and liposomes.

    Science.gov (United States)

    Lu, Cui-Tao; Zhao, Ying-Zheng; Gao, Hui-Sheng; Tian, Ji-Lai; Zhou, Zhi-Cai; Zhao, Gang-Tao; Tang, Qin-Qin; Jin, Zhuo; Xu, Yan-Yan; Huang, Pin-Tong; Han, Jing; Wang, Liang; Li, Xiao-Kun

    2010-01-01

    This work was to compare the encapsulation efficiency and ultrasound-triggered release for protein between microbubbles and liposomes. Bovine serum albumin (BSA) was used as a model. Final ratios between BSA and HPC in microbubbles and liposomes were 1:5, 1:7 and 1:10, respectively. Morphologic characteristics and contrast enhancement of loaded microbubbles and liposomes were measured. Encapsulation efficiency and ultrasound-stimulated release profile were detected. The mean size of loaded microbubbles and liposomes was 3.4 microm and 1.7 microm, respectively. Encapsulation efficiency of microbubbles had an inverse relationship with the ratio between BSA and HPC, while loaded liposomes remained nearly unchanged in the designed range of the ratio between BSA and HPC. Microbubbles resulted in significant enhancement of CnTi images. After ultrasound, more than 90% of the entrapped BSA was released from microbubbles, but less than 5% of BSA released from liposomes. Microbubbles are a promising delivery system for proteins.

  4. Quantifying linguistic coordination

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Tylén, Kristian

    ). We employ nominal recurrence analysis (Orsucci et al 2005, Dale et al 2011) on the decision-making conversations between the participants. We report strong correlations between various indexes of recurrence and collective performance. We argue this method allows us to quantify the qualities......Language has been defined as a social coordination device (Clark 1996) enabling innovative modalities of joint action. However, the exact coordinative dynamics over time and their effects are still insufficiently investigated and quantified. Relying on the data produced in a collective decision...

  5. Quantifying the accuracy of the tumor motion and area as a function of acceleration factor for the simulation of the dynamic keyhole magnetic resonance imaging method

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Danny; Pollock, Sean; Keall, Paul, E-mail: paul.keall@sydney.edu.au [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006 (Australia); Greer, Peter B. [School of Mathematical and Physical Sciences, University of Newcastle, Newcastle, NSW 2308, Australia and Department of Radiation Oncology, Calvary Mater Newcastle Hospital, Newcastle, NSW 2298 (Australia); Kim, Taeho [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23219 (United States)

    2016-05-15

    Purpose: The dynamic keyhole is a new MR image reconstruction method for thoracic and abdominal MR imaging. To date, this method has not been investigated with cancer patient magnetic resonance imaging (MRI) data. The goal of this study was to assess the dynamic keyhole method for the task of lung tumor localization using cine-MR images reconstructed in the presence of respiratory motion. Methods: The dynamic keyhole method utilizes a previously acquired a library of peripheral k-space datasets at similar displacement and phase (where phase is simply used to determine whether the breathing is inhale to exhale or exhale to inhale) respiratory bins in conjunction with central k-space datasets (keyhole) acquired. External respiratory signals drive the process of sorting, matching, and combining the two k-space streams for each respiratory bin, thereby achieving faster image acquisition without substantial motion artifacts. This study was the first that investigates the impact of k-space undersampling on lung tumor motion and area assessment across clinically available techniques (zero-filling and conventional keyhole). In this study, the dynamic keyhole, conventional keyhole and zero-filling methods were compared to full k-space dataset acquisition by quantifying (1) the keyhole size required for central k-space datasets for constant image quality across sixty four cine-MRI datasets from nine lung cancer patients, (2) the intensity difference between the original and reconstructed images in a constant keyhole size, and (3) the accuracy of tumor motion and area directly measured by tumor autocontouring. Results: For constant image quality, the dynamic keyhole method, conventional keyhole, and zero-filling methods required 22%, 34%, and 49% of the keyhole size (P < 0.0001), respectively, compared to the full k-space image acquisition method. Compared to the conventional keyhole and zero-filling reconstructed images with the keyhole size utilized in the dynamic keyhole

  6. Investigating Forest Harvest Effects on DOC Concentration and Quality: An In Situ, High Resolution Approach to Quantifying DOC Export Dynamics

    Science.gov (United States)

    Jollymore, A. J.; Johnson, M. S.; Hawthorne, I.

    2013-12-01

    Justification: Forest harvest effects on water quality can signal alterations in hydrologic and ecologic processes incurred as a result of forest harvest activities. Organic matter (OM), specifically dissolved organic carbon (DOC), plays a number of important roles mediating UV-light penetration, redox reactivity and microbial activity within aquatic ecosystems. Quantification of DOC is typically pursued via grab sampling followed by chemical or spectrophotometric analysis, limiting the temporal resolution obtained as well as the accuracy of export calculations. The advent of field-deployable sensors capable of measuring DOC concentration and certain quality characteristics in situ provides the ability to observe dynamics at temporal scales necessary for accurate calculation of DOC flux, as well as the observation of dynamic changes in DOC quality on timescales impossible to observe through grab sampling. Methods: This study utilizes a field deployable UV-Vis spectrophotometer (spectro::lyzer, s::can, Austria) to investigate how forest harvest affects DOC export. The sensor was installed at an existing hydrologic monitoring site at the outlet of a headwater stream draining a small (91 hectare) second growth Douglasfir-dominated catchment near Campbell River on Vancouver Island, British Columbia. Measurement began late in 2009, prior to forest harvest and associated activities such as road building (which commenced in October 2010 and ended in early 2011), and continues to present. During this time - encompassing the pre, during and post-harvest conditions - the absorbance spectrum of stream water from 200 to 750 nm was measured. DOC concentration and spectroscopic indices related to DOC quality (including SUVA, which relates to the concentration of aromatic carbon, and spectral slope) were subsequently calculated for each spectra obtained at 30-minute intervals. Results and conclusions: High frequency measurements of DOC show that overall export of OM increased in

  7. A co-flow-focusing monodisperse microbubble generator

    KAUST Repository

    Zhang, Jiaming

    2014-02-14

    We use a simple and inexpensive microfluidic device, which is based on microscope glass slides and two tapered glass capillaries, to produce monodisperse microbubbles. The innermost capillary used for transporting the gas is inserted into the second capillary, with its 2 μm sharp tip aligned with the center of the converging-diverging throat of the second capillary. This configuration provides a small and smooth gas flow rate, and a high velocity gradient at the tube outlet. Highly monodisperse microbubbles with diameters ranging from 3.5 to 60 microns have been successfully produced at a rate of up to 40 kHz. A simple scaling law, which is based on the capillary number and liquid-to-gas flow rate ratio, successfully predicts the bubble size. © 2014 IOP Publishing Ltd.

  8. Targeted drug delivery by ultrasound-triggered margination of microbubbles

    CERN Document Server

    Guckenberger, Achim

    2016-01-01

    The ideal agent for targeted drug delivery should stay away from the biochemically active walls of the blood vessels during circulation. However, upon reaching its target it should attain a near-wall position. Though seemingly contradictory, we show that coated microbubbles (ultrasound contrast agents) possess precisely these two properties. Using numerical simulations we find that application of a localized ultrasound pulse at the target organ triggers their rapid migration from the vessel center toward the endothelial wall. This ultrasound-triggered margination is due to hydrodynamic interactions between the red blood cells and the oscillating bubbles. Importantly, we find that the effect is very robust, existing even if the duration in the stiff state is five times lower than the opposing time in the soft state. Our results might also explain why recent in-vivo studies found strongly enhanced drug uptake by co-administration of microbubbles with classical drug delivery agents.

  9. Micro-Bubble Experiments at the Van de Graaff Accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Z. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Wardle, Kent E. [Argonne National Lab. (ANL), Argonne, IL (United States); Quigley, K. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Gromov, Roman [Argonne National Lab. (ANL), Argonne, IL (United States); Youker, A. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Makarashvili, Vakhtang [Argonne National Lab. (ANL), Argonne, IL (United States); Bailey, James [Argonne National Lab. (ANL), Argonne, IL (United States); Stepinski, D. C. [Argonne National Lab. (ANL), Argonne, IL (United States); Chemerisov, S. D. [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, G. F. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-02-01

    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 (O2 + H2) data were collected. The micro-bubble experiments at VDG indicate that the design of the full-scale bubble experiments at the LINAC is reasonable.

  10. Quantifying transient 3D dynamical phenomena of single mRNA particles in live yeast cell measurements.

    Science.gov (United States)

    Calderon, Christopher P; Thompson, Michael A; Casolari, Jason M; Paffenroth, Randy C; Moerner, W E

    2013-12-12

    Single-particle tracking (SPT) has been extensively used to obtain information about diffusion and directed motion in a wide range of biological applications. Recently, new methods have appeared for obtaining precise (10s of nm) spatial information in three dimensions (3D) with high temporal resolution (measurements obtained every 4 ms), which promise to more accurately sense the true dynamical behavior in the natural 3D cellular environment. Despite the quantitative 3D tracking information, the range of mathematical methods for extracting information about the underlying system has been limited mostly to mean-squared displacement analysis and other techniques not accounting for complex 3D kinetic interactions. There is a great need for new analysis tools aiming to more fully extract the biological information content from in vivo SPT measurements. High-resolution SPT experimental data has enormous potential to objectively scrutinize various proposed mechanistic schemes arising from theoretical biophysics and cell biology. At the same time, methods for rigorously checking the statistical consistency of both model assumptions and estimated parameters against observed experimental data (i.e., goodness-of-fit tests) have not received great attention. We demonstrate methods enabling (1) estimation of the parameters of 3D stochastic differential equation (SDE) models of the underlying dynamics given only one trajectory; and (2) construction of hypothesis tests checking the consistency of the fitted model with the observed trajectory so that extracted parameters are not overinterpreted (the tools are applicable to linear or nonlinear SDEs calibrated from nonstationary time series data). The approach is demonstrated on high-resolution 3D trajectories of single ARG3 mRNA particles in yeast cells in order to show the power of the methods in detecting signatures of transient directed transport. The methods presented are generally relevant to a wide variety of 2D and 3D SPT

  11. Parametric study and simulation of microbubble column flotation

    OpenAIRE

    1991-01-01

    A study based on a statistically designed set of experiments (Box-Behnken design) has been conducted to determine the optimum conditions for advanced physical fine coal cleaning using microbubble column flotation. The dependent variables in these experiments were mass yield and product quality (ash, sulfur and btu), while the independent variables were feed solids content, collector dosage, frother dosage, feed rate, aeration rate, and wash water rate. The most important operating parameters ...

  12. Microbubbles as drug delivery systems in cerebrovascular diseases.

    Science.gov (United States)

    Spinelli, Mariacarmela; Demitri, Christian; Sannino, Alessandro; Peruzzotti-Jametti, Luca; Bacigaluppi, Marco; Comi, Giancarlo; Corea, Francesco

    2009-11-01

    The field of neurovascular ultrasound is growing rapidly with new applications. While ultrasound contrast agents were initially used to overcome poor transcranial bone windows for identification of cerebral arteries, newgeneration microbubbles in combination with innovative contrast-specific ultrasound techniques now enable potential therapeutic procedures. This article will provide a review of recent and emerging developments along with patents in ultrasound technology and contrast-specific therapeutic techniques for cerebrovascular patients.

  13. Microbubbles-Assisted Ultrasound Triggers the Release of Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Yuana Yuana

    2017-07-01

    Full Text Available Microbubbles-assisted ultrasound (USMB has shown promise in improving local drug delivery. The formation of transient membrane pores and endocytosis are reported to be enhanced by USMB, and they contribute to cellular drug uptake. Exocytosis also seems to be linked to endocytosis upon USMB treatment. Based on this rationale, we investigated whether USMB triggers exocytosis resulting in the release of extracellular vesicles (EVs. USMB was performed on a monolayer of head-and-neck cancer cells (FaDu with clinically approved microbubbles and commonly used ultrasound parameters. At 2, 4, and 24 h, cells and EV-containing conditioned media from USMB and control conditions (untreated cells, cells treated with microbubbles and ultrasound only were harvested. EVs were measured using flow cytometric immuno-magnetic bead capture assay, immunogold electron microscopy, and western blotting. After USMB, levels of CD9 exposing-EVs significantly increased at 2 and 4 h, whereas levels of CD63 exposing-EVs increased at 2 h. At 24 h, EV levels were comparable to control levels. EVs released after USMB displayed a heterogeneous size distribution profile (30–1200 nm. Typical EV markers CD9, CD63, and alix were enriched in EVs released from USMB-treated FaDu cells. In conclusion, USMB treatment triggers exocytosis leading to the release of EVs from FaDu cells.

  14. Real-time two-dimensional imaging of microbubble cavitation

    Science.gov (United States)

    Vignon, Francois; Shi, W. T.; Powers, J. E.; Liu, J.; Drvol, L.; Lof, J.; Everbach, C.; Gao, S.; Xie, F.; Porter, T.

    2012-10-01

    Ultrasound cavitation of microbubble contrast agents has a potential for therapeutic applications, including sonothrombolysis in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (e.g. stable versus inertial forms of cavitation) and intensity in and around a treatment area. Acoustic Passive Cavitation Detectors (PCDs) have been used but do not provide spatial information. This paper presents a prototype of a 2D cavitation imager capable of producing images of the dominant cavitation state and intensity in a region of interest at a frame rate of 0.6Hz. The system is based on a modified ultrasound scanner (iE33, Philips) with a sector imaging probe (S5-1). Cavitation imaging is based on the spectral analysis of the acoustic signal radiated by the cavitating microbubbles: ultraharmonics of the excitation frequency indicate stable cavitation, while noise bands indicate inertial cavitation. The system demonstrates the capability to robustly identify stable and inertial cavitation thresholds of Definity microbubbles (Lantheus) in a vessel phantom through 3 ex-vivo human temporal bones, as well as to spatially map cavitation activities.

  15. Effect of ultrasound on adherent microbubble contrast agents.

    Science.gov (United States)

    Loughran, Jonathan; Sennoga, Charles; J Eckersley, Robert; Tang, Meng-Xing

    2012-11-01

    An investigation into the effect of clinical ultrasound exposure on adherent microbubbles is described. A flow phantom was constructed in which targeted microbubbles were attached using biotin-streptavidin linkages. Microbubbles were insonated by broadband imaging pulses (centred at 2.25 MHz) over a range of pressures (peak negative pressure (PNP) = 60-375 kPa). Individual adherent bubbles were observed optically and classified as either being isolated or with a single neighbouring bubble. It is found that bubble detachment and deflation are two significant effects, even during low amplitude ultrasound exposure. Specifically, while at very low acoustic pressure (PNP bubbles were not affected, at medium pressure (151 kPa bubbles detached and at higher pressures (301 kPa bubbles detached. In addition, more than 50% of the bubbles underwent deflation at pressures between 301 and 375 kPa. At pressures between 226 and 300 kPa, more adherent bubbles detached when there was a neighbouring bubble, suggesting the role of multiple scattering and secondary Bjerknes force on bubble detachment. The flow shear, primary and secondary Bjerknes forces exerted on each bubble were calculated and compared to the estimated forces acting on the bubble due to oscillations. The oscillation force is shown to be much higher than other forces. The mechanisms of bubble detachment are discussed.

  16. Portable Sensor for Detecting Microbubbles in Real Time to Prevent Decompression Sickness for Safe Diving During Subaquatic Navy Activities

    Science.gov (United States)

    2015-03-17

    Contains Proprietary information Final Report: Portable Sensor for Detecting Microbubbles in Real Time to Prevent Decompression Sickness for Safe Diving ...Portable Sensor for Detecting Microbubbles in Real Time to Prevent Decompression Sickness for Safe Diving During Subaquatic Navy Activities Report Title The...Portable Sensor for Detecting Microbubbles in Real Time to Prevent Decompression Sickness for Safe Diving During Subaquatic Navy Activities Final

  17. 87Sr/86Sr as a quantitative geochemical proxy for 14C reservoir age in dynamic, brackish waters: assessing applicability and quantifying uncertainties.

    Science.gov (United States)

    Lougheed, Bryan; van der Lubbe, Jeroen; Davies, Gareth

    2016-04-01

    Accurate geochronologies are crucial for reconstructing the sensitivity of brackish and estuarine environments to rapidly changing past external impacts. A common geochronological method used for such studies is radiocarbon (14C) dating, but its application in brackish environments is severely limited by an inability to quantify spatiotemporal variations in 14C reservoir age, or R(t), due to dynamic interplay between river runoff and marine water. Additionally, old carbon effects and species-specific behavioural processes also influence 14C ages. Using the world's largest brackish water body (the estuarine Baltic Sea) as a test-bed, combined with a comprehensive approach that objectively excludes both old carbon and species-specific effects, we demonstrate that it is possible to use 87Sr/86Sr ratios to quantify R(t) in ubiquitous mollusc shell material, leading to almost one order of magnitude increase in Baltic Sea 14C geochronological precision over the current state-of-the-art. We propose that this novel proxy method can be developed for other brackish water bodies worldwide, thereby improving geochronological control in these climate sensitive, near-coastal environments.

  18. Quantifying the impacts of land surface schemes and dynamic vegetation on the model dependency of projected changes in surface energy and water budgets

    Science.gov (United States)

    Yu, Miao; Wang, Guiling; Chen, Haishan

    2016-03-01

    Assessing and quantifying the uncertainties in projected future changes of energy and water budgets over land surface are important steps toward improving our confidence in climate change projections. In this study, the contribution of land surface models to the inter-GCM variation of projected future changes in land surface energy and water fluxes are assessed based on output from 19 global climate models (GCMs) and offline Community Land Model version 4 (CLM4) simulations driven by meteorological forcing from the 19 GCMs. Similar offline simulations using CLM4 with its dynamic vegetation submodel are also conducted to investigate how dynamic vegetation feedback, a process that is being added to more earth system models, may amplify or moderate the intermodel variations of projected future changes. Projected changes are quantified as the difference between the 2081-2100 period from the Representative Concentration Pathway 8.5 (RCP8.5) future experiment and the 1981-2000 period from the historical simulation. Under RCP8.5, projected changes in surface water and heat fluxes show a high degree of model dependency across the globe. Although precipitation is very likely to increase in the high latitudes of the Northern Hemisphere, a high degree of model-related uncertainty exists for evapotranspiration, soil water content, and surface runoff, suggesting discrepancy among land surface models (LSMs) in simulating the surface hydrological processes and snow-related processes. Large model-related uncertainties for the surface water budget also exist in the Tropics including southeastern South America and Central Africa. These uncertainties would be reduced in the hypothetical scenario of a single near-perfect land surface model being used across all GCMs, suggesting the potential to reduce uncertainties through the use of more consistent approaches toward land surface model development. Under such a scenario, the most significant reduction is likely to be seen in the

  19. PREPARATION OF POLYELECTROLYTE MULTILAYER COATED MICROBUBBLES FOR USE AS ULTRASOUND CONTRAST AGENT

    Institute of Scientific and Technical Information of China (English)

    Zhan-wen Xing; Heng-te Ke; Shao-qin Liu; Zhi-fei Dai; Jin-rui Wang; Ji-bin Liu

    2008-01-01

    Objective To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent (UCA) and evaluate its effects in ultrasonic imaging on normal rabbit's fiver parenchyma.Methoda Pcrfluorocarbon (PFC)-containing microbubbles (ST68-PFC) were prepared by sonication based on surfactant ( Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbnbbles were coated using oppositely charged polyclectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction.The enhancement effects in ultrasonic imaging on normal rabbit's liver parenchyma were assessed.Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit's liver parenchyma.Conclnsions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function,has no obvious difference in enhancement effects compared with the pre-modified microbnbbles. The polymers with chemically active groups ( such as amino group and carboxyl group) can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.

  20. Understanding the Structure and Mechanism of Formation of a New Magnetic Microbubble Formulation

    Directory of Open Access Journals (Sweden)

    Joshua Owen, Bin Zhou, Paul Rademeyer, Meng-Xing Tang, Quentin Pankhurst, Robert Eckersley, Eleanor Stride

    2012-01-01

    Full Text Available Magnetic nanoparticles and ultrasound contrast agents have both been used as vehicles for therapeutic delivery. More recently, magnetic microbubbles have been developed as a new theranostic agent which combines the advantages of the individual carriers and overcomes many of their limitations. In a previous study of gene delivery using magnetic microbubbles, it was found that a combination of magnetic liquid droplets and non-magnetic phospholipid microbubbles produced higher transfection rates than magnetic microbubbles. The reasons for this were not fully understood, however. The aim of this study was to investigate the hypothesis that conjugation between the droplets and the microbubbles occurred. A combination of optical and fluorescence microscopy and ultrasound imaging studies in a flow phantom were performed. No interaction between magnetic droplets and microbubbles was observed under optical microscopy but the results from the fluorescence and acoustic imaging indicated that magnetic droplets and microbubbles do indeed combine to form a new magnetically and acoustically responsive particle. Theoretical calculations indicate that the driving force of the interaction is the relative surface energy and thus thermodynamic stability of the microbubbles and the droplets. The new particles were resistant to centrifugation, of comparable echogenicity to conventional ultrasound contrast agents and could be retained by a magnetic field (0.2T in a flow phantom at centre line velocities of ~6 cm s-1 and shear rates of ~60 s -1.

  1. Use of intravital microscopy to study the microvascular behavior of microbubble-based ultrasound contrast agents.

    Science.gov (United States)

    Schneider, Michel; Broillet, Anne; Tardy, Isabelle; Pochon, Sibylle; Bussat, Philippe; Bettinger, Thierry; Helbert, Alexandre; Costa, Maria; Tranquart, François

    2012-04-01

    The study describes the use of intravital microscopy (IVM) to assess the behavior of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents. IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle, and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Nontargeted UCAs (SonoVue(®) and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence, and observe their behavior in the blood circulation. Intravenous and intra-arterial injections of high doses of UCAs did not modify the local microvascular hemodynamics. No microbubble coalescence and no increased size were observed. Adhesion of some microbubbles to leukocytes was observed in various microcirculation models. Microbubbles are captured by Kupffer cells in the liver. Targeted microbubbles were shown to adhere specifically to endothelial receptors without compromising local blood flow. These results support the safety of both targeted and nontargeted UCAs as no microvascular flow alteration or plugging of microvessels were observed. They confirm that binding observed with targeted microbubbles are due to the binding of these microbubbles to specific endothelial receptors. © 2012 John Wiley & Sons Ltd.

  2. Factors that affect the efficiency of antisense oligodeoxyribonucleotide transfection by insonated gas-filled lipid microbubbles

    Science.gov (United States)

    Zhao, Ying-Zheng; Lu, Cui-Tao

    2008-03-01

    Objective: To investigate the factors that affect the efficiency of antisense oligodeoxyribonucleotide(AS-ODNs) transfection by insonated gas-filled lipid microbubbles. Methods: Lipid microbubbles filled with two types of gases-air and C3F8, were prepared respectively. An AS-ODNs sequence HA824 and a breast cancer cell line SK-BR-3 were used to define the various operating variables determining the transfection efficiency of insonated microbubbles. Two mixing methods, three levels of mixing speed, different mixing durations and various ultrasound initiation time after mixing were examined respectively. Transfection efficiency was detected by fluorescence microscopy. Results: C3F8 microbubbles gave higher levels of AS-ODNs transfection efficiency than air microbubbles in all test conditions. Transfection efficiency resulted from mixing method A (incubation of HA824 and microbubbles before mixing cells) did not show significant difference with that of mixing method B (without incubation of HA824 and microbubbles before mixing cells). Mixing speed, duration of mixing and ultrasound initiation time after mixing were central to determining HA824 transfection efficiency in vitro. The optimum parameters for SK-BR-3 cells were found at a mixing speed of 40-50 rpm for 30-60 s with less than 60 s delay before ultrasound. Conclusion: Ultrasound-mediated AS-ODNs transfection enhanced by C3F8-filled lipid microbubbles represents an effective avenue for AS-ODNs transfer.

  3. Factors that affect the efficiency of antisense oligodeoxyribonucleotide transfection by insonated gas-filled lipid microbubbles

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Yingzheng [General Hospital of Beijing Military Command of PLA, Department of Clinical Pharmacology (China)], E-mail: lctuua@yahoo.com.cn; Lu Cuitao [Madam Medical Management Group (China)

    2008-03-15

    Objective: To investigate the factors that affect the efficiency of antisense oligodeoxyribonucleotide(AS-ODNs) transfection by insonated gas-filled lipid microbubbles. Methods: Lipid microbubbles filled with two types of gases-air and C{sub 3}F{sub 8}, were prepared respectively. An AS-ODNs sequence HA824 and a breast cancer cell line SK-BR-3 were used to define the various operating variables determining the transfection efficiency of insonated microbubbles. Two mixing methods, three levels of mixing speed, different mixing durations and various ultrasound initiation time after mixing were examined respectively. Transfection efficiency was detected by fluorescence microscopy. Results: C{sub 3}F{sub 8} microbubbles gave higher levels of AS-ODNs transfection efficiency than air microbubbles in all test conditions. Transfection efficiency resulted from mixing method A (incubation of HA824 and microbubbles before mixing cells) did not show significant difference with that of mixing method B (without incubation of HA824 and microbubbles before mixing cells). Mixing speed, duration of mixing and ultrasound initiation time after mixing were central to determining HA824 transfection efficiency in vitro. The optimum parameters for SK-BR-3 cells were found at a mixing speed of 40-50 rpm for 30-60 s with less than 60 s delay before ultrasound. Conclusion: Ultrasound-mediated AS-ODNs transfection enhanced by C{sub 3}F{sub 8}-filled lipid microbubbles represents an effective avenue for AS-ODNs transfer.

  4. Characterizing the subharmonic response of phospholipid-coated microbubbles for carotid imaging.

    Science.gov (United States)

    Faez, Telli; Emmer, Marcia; Docter, Margreet; Sijl, Jeroen; Versluis, Michel; de Jong, Nico

    2011-06-01

    The subharmonic vibration of BR14 (Bracco Research S.A., Geneva, Switzerland) contrast agent microbubbles is investigated within the preferable frequency range for carotid ultrasound imaging (8-12 MHz). The response of the bubbles was recorded optically with an ultra-fast recording camera (Brandaris 128) at three acoustic pressures (50, 100 and 120 kPa). The vibration of the microbubbles was measured as a function of the excitation frequency and its frequency content was determined. Among 390 recordings, 40% showed subharmonic oscillations. It was observed that for smaller microbubbles (diameter subharmonic response increases for increasing pressures (shell hardening) opposite to what has been reported for larger microbubbles (3 μm < diameter < 15 μm). These findings are well predicted by the model proposed by Marmottant et al. (2005) after including the dilatational shell viscosity of the microbubbles measured by Van der Meer et al. (2007), which indicates a marked shear-thinning behavior of the phospholipid shell.

  5. The influence of compliant boundary proximity on the fundamental and subharmonic emissions from individual microbubbles.

    Science.gov (United States)

    Helfield, Brandon L; Leung, Ben Y C; Goertz, David E

    2014-07-01

    The proximity of a solid-liquid boundary has been theoretically predicted to affect nonlinear microbubble emissions, but to date there has been no experimental validation of this effect. In this study, individual microbubbles (n = 15) were insonicated at f = 11 MHz as a function of offset distance from a compliant (agarose) planar boundary by employing an optical trapping apparatus. It was found that fundamental scattering increases while subharmonic scattering decreases as the microbubble approaches the boundary. Although a microbubble-boundary model can predict the qualitative trends observed for a subset of encapsulation properties, further modeling efforts are required to completely model compliant boundary-microbubble interactions.

  6. Self-assembled liposome-loaded microbubbles: The missing link for safe and efficient ultrasound triggered drug-delivery.

    Science.gov (United States)

    Geers, Bart; Lentacker, Ine; Sanders, Niek N; Demeester, Joseph; Meairs, Stephen; De Smedt, Stefaan C

    2011-06-10

    Liposome-loaded microbubbles have been recently introduced as a promising drug delivery platform for ultrasound guided drug delivery. In this paper we design liposome-loaded (lipid-shelled) microbubbles through the simple self-assembly of the involved compounds in a single step process. We thoroughly characterized the liposome-loading of the microbubbles and evaluated the cell killing efficiency of this material using doxorubicin (DOX) as a model drug. Importantly, we observed that the DOX liposome-loaded microbubbles allowed killing of melanoma cells even at very low doses of DOX. These findings clearly prove the potential of liposome-loaded microbubbles for ultrasound targeted drug delivery to cancer tissues.

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

    Science.gov (United States)

    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 CO2 microbubbles (from tip side to base side) in CO2-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 CO2 microbubbles for collection and transportation. We believe that this approach provides a simple and valid way to remove microbubbles.

  8. High heat flux transport by microbubble emission boiling

    Science.gov (United States)

    Suzuki, Koichi

    2007-10-01

    In highly subcooled flow boiling, coalescing bubbles on the heating surface collapse to many microbubbles in the beginning of transition boiling and the heat flux increases higher than the ordinary critical heat flux. This phenomenon is called Microbubble Emission Boiling, MEB. It is generated in subcooled flow boiling and the maximum heat flux reaches about 1 kW/cm2(10 MW/m2) at liquid subcooling of 40 K and liquid velocity of 0.5 m/s for a small heating surface of 10 mm×10 mm which is placed at the bottom surface of horizontal rectangular channel. The high pressure in the channel is observed at collapse of the coalescing bubbles and it is closely related the size of coalescing bubbles. Periodic pressure waves are observed in MEB and the heat flux increases linearly in proportion to the pressure frequency. The frequency is considered the frequency of liquid-solid exchange on the heating surface. For the large sized heating surface of 50 mm length×20 mm width, the maximum heat flux obtained is 500 W/cm2 (5 MW/m2) at liquid subcooling of 40 K and liquid velocity of 0.5 m/s. This is considerably higher heat flux than the conventional cooling limit in power electronics. It is difficult to remove the high heat flux by MEB for a longer heating surface than 50 mm by single channel type. A model of advanced cooling device is introduced for power electronics by subcooled flow boiling with impinging jets. Themaxumum cooling heat flux is 500 W/cm2 (5 MW/m2). Microbubble emission boiling is useful for a high heat flux transport technology in future power electronics used in a fuel-cell power plant and a space facility.

  9. Microbubble enhanced ozonation process for advanced treatment of wastewater produced in acrylic fiber manufacturing industry

    KAUST Repository

    Zheng, Tianlong

    2015-02-02

    This work investigated microbubble-ozonation for the treatment of a refractory wet-spun acrylic fiber wastewater in comparison to macrobubble-ozonation. CODcr, NH3-N, and UV254 of the wastewater were removed by 42%, 21%, and 42%, respectively in the microbubble-ozonation, being 25%, 9%, and 35% higher than the removal rates achieved by macrobubble-ozonation at the same ozone dose. The microbubbles (with average diameter of 45μm) had a high concentration of 3.9×105 counts/mL at a gas flow rate of 0.5L/min. The gas holdup, total ozone mass-transfer coefficient, and average ozone utilization efficiency in the microbubble-ozonation were 6.6, 2.2, and 1.5 times higher than those of the macrobubble-ozonation. Greater generation of hydroxyl radicals and a higher zeta potential of the bubbles were also observed in the microbubble ozonation process. The biodegradability of the wastewater was also significantly improved by microbubble-ozonation, which was ascribed to the enhanced degradation of alkanes, aromatic compounds, and the many other bio-refractory organic compounds in the wastewater. Microbubble-ozonation can thus be a more effective treatment process than traditional macrobubble-ozonation for refractory wastewater produced by the acrylic fiber manufacturing industry.

  10. Elevation of plasma membrane permeability upon laser irradiation of extracellular microbubbles.

    Science.gov (United States)

    Zhou, Yu; Zhou, Xi-Yuan; Wang, Zhi-Gang; Zhu, Ye-Feng; Li, Pan

    2010-07-01

    Laser-mediated gene transfection has received much attention as a new method for targeted gene therapy because of the high controllability of laser energy and direction. In this report, we describe a combination laser-microbubble system that enables membrane-impermeable molecules to penetrate cell membranes. The main theories we apply are optical breakdown and photoacoustic generation, which are induced by laser irradiation. Firstly, different types of laser light (Ar-green, Novus Varia poly-wavelength and Nd:YAG laser) were adopted to blast liposome microbubble contrast medium; subsequently, the Nd:YAG laser (1064 nm, 4 ns), which could successfully blast microbubbles, and ultrasound were used in combination to irradiate a mixture of liposome microbubbles and retinoblastoma (Rb) cells. After irradiation, membrane permeability was evaluated by flow cytometric assay using propidium iodide (PI) and fluorescein diacetate (FDA). The proportion of permeabilized resealed cells was affected by changes in the light energy. All of the Nd:YAG laser, Nd:YAG combination laser-microbubble and combination ultrasound-microbubble systems were able to permeabilize the Rb cells. These results suggest that this combination laser-microbubble system is a new means of delivering exogenous materials into living cells.

  11. Degradation of methyl orange using short-wavelength UV irradiation with oxygen microbubbles.

    Science.gov (United States)

    Tasaki, Tsutomu; Wada, Tsubasa; Fujimoto, Kanji; Kai, Shinji; Ohe, Kaoru; Oshima, Tatsuya; Baba, Yoshinari; Kukizaki, Masato

    2009-03-15

    A novel wastewater treatment technique using 8 W low-pressure mercury lamps in the presence of uniform-sized microbubbles (diameter = 5.79 microm) was investigated for the decomposition of methyl orange as a model compound in aqueous solution. Photodegradation experiments were conducted with a BLB black light blue lamp (365 nm), a UV-C germicidal lamp (254 nm) and an ozone lamp (185 nm+254 nm) both with and without oxygen microbubbles. The results show that the oxygen microbubbles accelerated the decolorization rate of methyl orange under 185+254 nm irradiation. In contrast, the microbubbles under 365 and 254 nm irradiation were unaffected on the decolorization of methyl orange. It was found that the pseudo-zero order decolorization reaction constant in microbubble system is 2.1 times higher than that in conventional large bubble system. Total organic carbon (TOC) reduction rate of methyl orange was greatly enhanced by oxygen microbubble under 185+254 nm irradiation, however, TOC reduction rate by nitrogen microbubble was much slower than that with 185+254 nm irradiation only. Possible reaction mechanisms for the decolorization and mineralization of methyl orange both with oxygen and nitrogen mirobubbles were proposed in this study.

  12. Flow quantification with nakagami parametric imaging for suppressing contrast microbubbles attenuation.

    Science.gov (United States)

    Gu, Xiaolin; Wei, Min; Zong, Yujin; Jiang, Hujie; Wan, Mingxi

    2013-04-01

    Flow quantification with contrast-enhanced ultrasound is still limited by the effects of contrast microbubble attenuation. Nakagami parametric imaging (NPI) based on the m parameter, which is related to the statistical property of echo envelope, is implemented to suppress contrast attenuation. Flow velocity (FV) and volumetric flow rate (VFR) are estimated through the least square fitting of burst depletion kinetic model to time m parameter curves (TMCs). A non-recirculating flow phantom is imaged as contrast microbubbles are infused at 10, 15, 20, 25, and 30 mL/min. Contrast microbubbles with two different concentrations are used to generate variations of contrast microbubble attenuation. The results suggest that 4 × 4 mm(2) is the optimal size of a sliding window of NPI for flow quantification under current experiment condition. At a lower microbubble concentration, the FV calculated from TMCs correlates strongly with actual FV in both unattenuated (R(2) = 0.97; p < 0.01) and attenuated regions (R(2) = 0.92; p < 0.01) within phantom. And there is a strong correlation (R(2) = 0.98; p < 0.01; slope = 0.96; intercept = 0.68) between VFR calculated from TMCs and actual VFR within the whole phantom. Similar results are obtained at higher microbubble concentrations. Compared with conventional ultrasound imaging that is intensity dependent, NPI achieves better performance on flow quantification in the presence of contrast microbubble attenuation.

  13. Quantifying the flow dynamics of supercritical CO2-water displacement in a 2D porous micromodel using fluorescent microscopy and microscopic PIV

    Science.gov (United States)

    Kazemifar, Farzan; Blois, Gianluca; Kyritsis, Dimitrios C.; Christensen, Kenneth T.

    2016-09-01

    The multi-phase flow of liquid/supercritical CO2 and water (non-wetting and wetting phases, respectively) in a two-dimensional silicon micromodel was investigated at reservoir conditions (80 bar, 24 °C and 40 °C). The fluorescent microscopy and microscopic particle image velocimetry (micro-PIV) techniques were combined to quantify the flow dynamics associated with displacement of water by CO2 (drainage) in the porous matrix. To this end, water was seeded with fluorescent tracer particles, CO2 was tagged with a fluorescent dye and each phase was imaged independently using spectral separation in conjunction with microscopic imaging. This approach allowed simultaneous measurement of the spatially-resolved instantaneous velocity field in the water and quantification of the spatial configuration of the two fluid phases. The results, acquired with sufficient time resolution to follow the dynamic progression of both phases, provide a comprehensive picture of the flow physics during the migration of the CO2 front, the temporal evolution of individual menisci, and the growth of fingers within the porous microstructure. During that growth process, velocity jumps 20-25 times larger in magnitude than the bulk velocity were measured in the water phase and these bursts of water flow occurred both in-line with and against the bulk flow direction. These unsteady velocity events support the notion of pressure bursts and Haines jumps during pore drainage events as previously reported in the literature [1-3]. After passage of the CO2 front, shear-induced flow was detected in the trapped water ganglia in the form of circulation zones near the CO2-water interfaces as well as in the thin water films wetting the surfaces of the silicon micromodel. To our knowledge, the results presented herein represent the first quantitative spatially and temporally resolved velocity-field measurements at high pressure for water displacement by liquid/supercritical CO2 injection in a porous micromodel.

  14. Increasing of Blood-Brain Tumor Barrier Permeability through Transcellular and Paracellular Pathways by Microbubble-Enhanced Diagnostic Ultrasound in a C6 Glioma Model

    Science.gov (United States)

    Zhang, Jinlong; Liu, Heng; Du, Xuesong; Guo, Yu; Chen, Xiao; Wang, Shunan; Fang, Jingqin; Cao, Peng; Zhang, Bo; Liu, Zheng; Zhang, Weiguo

    2017-01-01

    Most of the anticancer agents cannot be efficiently delivered into the brain tumor because of the existence of blood-brain tumor barrier (BTB). The objective of this study was to explore the effect of microbubble-enhanced diagnostic ultrasound (MEUS) on the BTB permeability and the possible mechanism. Glioma-bearing rats were randomized into three groups as follows: the microbubble-enhanced continued diagnostic ultrasound (MECUS) group; the microbubble-enhanced intermittent diagnostic ultrasound (MEIUS) group and the control group. The gliomas were insonicated through the skull with a diagnostic ultrasound and injected with microbubbles through the tail veins. Evans Blue (EB) and dynamic contrast-enhanced-MRI were used to test changes in the BTB permeability. Confocal laser scanning microscopy was used to observe the deposition of the EB in the tumor tissues. The distribution and expression of junctional adhesion molecule-A (JAM-A) and calcium-activated potassium channels (KCa channels) were detected by a Western blot, qRT-PCR, and immunohistochemical staining. In the MEUS groups, the EB extravasation (11.0 ± 2.2 μg/g in MECUS group and 17.9 ± 2.3 μg/g in MEIUS group) exhibited a significant increase compared with the control group (5.3 ± 0.9 μg/g). The MEIUS group had more EB extravasation than the MECUS group. The Ktrans value of the dynamic contrast-enhanced-MRI in the MEUS groups was higher than that of the control group and correlated strongly with the EB extravasation in the tumor (R2 = 0.97). This showed that the Ktrans value might be a non-invasive method to evaluate the BTB permeability in rat glioma after microbubble-enhanced ultrasound treatment.Western blot, qRT-PCR and immunohistochemical staining revealed that MEUS increased the KCa channels expression and reduced JAM-A expression in glioma. This change was more obvious in the MEIUS group than in the MECUS group. The results demonstrated that MEUS effectively increased the BTB permeability in

  15. Microbubble formation and pinch-off scaling exponent in flow-focusing devices

    CERN Document Server

    van Hoeve, Wim; Versluis, Michel; Lohse, Detlef

    2011-01-01

    We investigate the gas jet breakup and the resulting microbubble formation in a microfluidic flow-focusing device using ultra high-speed imaging at 1 million frames/s. In recent experiments [Dollet et al., Phys. Rev. Lett. 100, 034504 (2008)] it was found that in the final stage of the collapse the radius of the neck scales with time with a 1/3 power-law exponent, which suggested that gas inertia and the Bernoulli suction effect become important. Here, ultra high-speed imaging was used to capture the complete bubble contour and quantify the gas flow through the neck. It revealed that the resulting decrease in pressure, due to Bernoulli suction, is too low to account for an accelerated pinch-off. The high temporal resolution images enable us to approach the final moment of pinch-off to within 1 {\\mu}s. We observe that the final moment of bubble pinch-off is characterized by a scaling exponent of 0.41 +/- 0.01. This exponent is approximately 2/5, which can be derived, based on the observation that during the co...

  16. Simulation of microbubble response to ambient pressure changes

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2008-01-01

    The theory on microbubbles clearly indicates a relation between the ambient pressure and the acoustic behavior of the bubble. The purpose of this study was to optimize the sensitivity of ambient pressure measurements, using the subharmonic component, through microbubble response simulations...... of 4.6 dB is observed when changing pov from 0 to 25 kPa. Increasing the pulse duration makes the reduction even more clear. For a pulse with 64 cycles, the reduction is 9.9 dB. This simulation is in good correspondence with measurement results presented by Shi et al. 1999, who found a linear reduction...... of 9.6 dB. Further simulations of Levovist show that also the shape and the acoustic pressure of the driving pulse are very important factors. The best pressure sensitivity of Levovist was found to be 0.88 dB/kPa. For Sonazoid, a sensitivity of 0.71 dB/kPa has been found, although the reduction...

  17. Ambient pressure sensitivity of microbubbles investigated through a parameter study

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

    Measurements on microbubbles clearly indicate a relation between the ambient pressure and the acoustic behavior of the bubble. The purpose of this study was to optimize the sensitivity of ambient pressure measurements, using the subharmonic component, through microbubble response simulations...... cycles driving pulse, a reduction of 4.6 dB is observed when changing pov from 0 to 25 kPa. Increasing the pulse duration makes the reduction even more clear. For a pulse with 64 cycles, the reduction is 9.9 dB. This simulation is in good correspondence with measurement results presented by Shi et al....... 1999, who found a linear reduction of 9.6 dB. Further simulations of Levovist show that also the shape and the acoustic pressure of the driving pulse are very important factors. The best pressure sensitivity of Levovist was found to be 0.88 dB/kPa. For Sonazoid, a sensitivity of 1.14 dB/kPa has been...

  18. Removal of dimethyl phthalate from water by ozone microbubbles.

    Science.gov (United States)

    Jabesa, Abdisa; Ghosh, Pallab

    2016-10-27

    This work investigates the removal of dimethyl phthalate (DMP) from water using ozone microbubbles in a pilot plant of 20 dm(3) capacity. Experiments were performed under various reaction conditions to examine the effects of the initial concentration of DMP, pH of the medium, ozone generation rate, and the role of H2O2 on the removal of DMP. The DMP present in water was effectively removed by the ozone microbubbles. The removal was effective in neutral and alkaline media. Increase in the initial concentration of the target pollutant negatively affected its removal efficiency. The removal efficiency dramatically increased from 1% to 99% when the ozone generation rate was increased from 0.28 to 1.94 mg s(-1) at pH 7. The total organic carbon measurements revealed that a complete mineralization of DMP was achieved within 1.8 ks at the high ozone feed rate. The use of t-butyl alcohol as the hydroxyl radical scavenger confirmed that the reaction between the target organic compound and ·OH radical dominated over its direct reaction with ozone. The reaction between DMP and ozone followed an overall second-order kinetics. The volumetric mass transfer coefficient of ozone in the reacting system and the enhancement factor increased with increasing initial concentration of DMP. Very low values of Hatta number were obtained at all initial concentrations of DMP and pH, which show that the mass transfer resistance was small.

  19. External laser locking using a pressure-tunable microbubble resonator

    CERN Document Server

    Madugani, Ramgopal; Le, Vu H; Ward, Jonathan M; Chormaic, Síle Nic

    2015-01-01

    The tunability of an optical cavity is an essential requirement for many areas of research especially for the rapidly progressing field of photonics. In particular, low-cost laser tuning methods and miniaturization of the optical components are desirable. By applying aerostatic pressure to the interior surface of a microbubble resonator, optical mode shift rates of around $58$ GHz/MPa are achieved. The micobubble can measure pressure with a limit of detection of $2\\times 10^{-4}$ MPa. Here we use the Pound-Drever-Hall technique, whereby a laser is locked to a whispering gallery mode (WGM) of the microbubble resonator, to show that linear tuning of the WGM and the corresponding locked laser display almost zero hysteresis. The long-term frequency stability of this tuning method for different input pressures is measured. The frequency noise of the WGM, measured over 10 minutes, with a maximum input pressure of 0.5 MPa has a standard deviation of 36 MHz.

  20. Water oxygenation by fluidic microbubble generator

    Directory of Open Access Journals (Sweden)

    Tesař V

    2014-03-01

    Full Text Available Oxygenation of water by standard means in waste water processing, in particular to improve the conditions for the micro-organisms that decompose organic wastes is rather ineffective. The classical approach to improvements – decreasing the size of the aerator exits - have already reached their limits. A recent new idea is to decrease the size of the generated air bubbles by oscillating the supplied air flow using fluidic oscillators. Authors made extensive performance measurements with an unusual high-frequency fluidic oscillator, designed to operate within the submersed aerator body. The performance was evaluated by the dynamic method of recording the oxygen concentration increase to saturation in the aerated water. Experiments proved the fluidic generator can demonstrably increase the aeration efficiency 4.22-times compared with the aeration from a plain end of a submerged air supply tube. Despite this significant improvement, the behaviour of the generator still provides an opportunity for further improvements.

  1. Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles.

    Science.gov (United States)

    Peyman, Sally A; Abou-Saleh, Radwa H; McLaughlan, James R; Ingram, Nicola; Johnson, Benjamin R G; Critchley, Kevin; Freear, Steven; Evans, J Anthony; Markham, Alexander F; Coletta, P Louise; Evans, Stephen D

    2012-11-01

    Micron sized, lipid stabilized bubbles of gas are of interest as contrast agents for ultra-sound (US) imaging and increasingly as delivery vehicles for targeted, triggered, therapeutic delivery. Microfluidics provides a reproducible means for microbubble production and surface functionalisation. In this study, microbubbles are generated on chip using flow-focussing microfluidic devices that combine streams of gas and liquid through a nozzle a few microns wide and then subjecting the two phases to a downstream pressure drop. While microfluidics has successfully demonstrated the generation of monodisperse bubble populations, these approaches inherently produce low bubble counts. We introduce a new micro-spray flow regime that generates consistently high bubble concentrations that are more clinically relevant compared to traditional monodisperse bubble populations. Final bubble concentrations produced by the micro-spray regime were up to 10(10) bubbles mL(-1). The technique is shown to be highly reproducible and by using multiplexed chip arrays, the time taken to produce one millilitre of sample containing 10(10) bubbles mL(-1) was ∼10 min. Further, we also demonstrate that it is possible to attach liposomes, loaded with quantum dots (QDs) or fluorescein, in a single step during MBs formation.

  2. Definition of contrast enhancement phases of the liver using a perfluoro-based microbubble agent, perflubutane microbubbles.

    Science.gov (United States)

    Shunichi, Sasaki; Hiroko, Iijima; Fuminori, Moriyasu; Waki, Hidehiko

    2009-11-01

    To define the contrast enhancement phases in the liver with perflubutane microbubbles, the liver enhancement time-intensity curves were investigated in 14 healthy volunteers. The agent was injected intravenously as a bolus and the liver was imaged with an ultrasound scanner as long as 4h after the injection. Time-intensity curves from the hepatic artery, the intrahepatic portal vein, the hepatic vein and the parenchyma of the liver were obtained from the liver ultrasound images. The arrival of the agent in the hepatic artery, the portal vein and the hepatic vein were visually distinguishable and the mean arrival times were 19.2, 24.3 and 32.2 s after the injection, respectively. The signal intensity in these vessels increased rapidly after the arrival of the contrast and gradually reverted to baseline after the peak. In contrast, within 5 min after the injection, the intensity in the parenchyma increased and reached a plateau, which persisted for at least 2h. The contrast enhancement phases in the liver with perflubutane microbubbles could be defined as two major phases-a vascular phase, in which the vessels are enhanced between 15 s and 10 min after injection, and a Kupffer phase, in which the parenchyma is enhanced 10 min after injection. The vascular phase is divided into three subphases: the arterial phase (15 to 45 s after injection); the portal phase (45 s to 1 min after injection); and the vasculo-Kupffer phase (1 to 10 min after injection).

  3. Targeted liposome-loaded microbubbles for cell-specific ultrasound-triggered drug delivery.

    Science.gov (United States)

    Geers, Bart; De Wever, Olivier; Demeester, Joseph; Bracke, Marc; De Smedt, Stefaan C; Lentacker, Ine

    2013-12-01

    One of the main problems in cancer treatment is disease relapse through metastatic colonization, which is caused by circulating tumor cells (CTCs). This work reports on liposome-loaded microbubbles targeted to N-cadherin, a cell-cell adhesion molecule expressed by CTCs. It is shown that such microbubbles can indeed bind to N-cadherin at the surface of HMB2 cells. Interestingly, in a mixture of cells with and without N-cadherin expression, binding of the liposome-loaded microbubbles mainly occurs to the N-cadherin-expressing cells. Importantly, applying ultrasound results in the intracellular delivery of a model drug (loaded in the liposomes) in the N-cadherin-expressing cells only. As described in this paper, such liposome-loaded microbubbles may find application as theranostics and in devices aimed for the specific killing of CTCs in blood.

  4. Blood flow contrast enhancement in optical coherence tomography using microbubbles: a phantom study

    Science.gov (United States)

    Assadi, Homa; Demidov, Valentin; Karshafian, Raffi; Douplik, Alexandre; Vitkin, I. Alex

    2016-03-01

    In this study gas microbubbles are investigated as intravascular OCT contrast agents. Agar+Intralipid scattering tissue-like phantoms with two embedded microtubes were fabricated to model vascular blood flow. One was filled with human blood, and the other with a mixture of human blood and microbubbles. Swept-source structural and speckle variance OCT images, as well as speckle decorrelation times, were evaluated under both stationary and flow conditions. Faster decorrelation times and higher image contrast were detected in the presence of microbubbles in all experiments, and the effect was largest for speckle variance OCT ~2.3x greater contrast under flow conditions. The feasibility of utilizing microbubbles for tissue hemodynamic investigations and for microvasculature contrast enhancement in OCT angiography thus appears promising.

  5. Tanscranial Threshold of Inertial Cavitation Induced by Diagnosticc Ultrasound and Microbubbles

    NARCIS (Netherlands)

    Liu, J.; Gao, S.; Porter, T.R.; Everbach, C; Shi, W.; Vignon, F.; Powers, J.; Lof, J.; Turner, J.; Xie, F.

    2011-01-01

    Background: Inertial cavitation may cause hazardous bioeffects whileusing ultrasound and microbubble mediated thrombolysis. The purposeof this study was to investigate the influence of ultrasound pulselength and temporal bone on inertial cavitation thresholds within the brain utilizing transtemporal

  6. Correlation between microbubble-induced acoustic cavitation and hemolysis in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhang Chun-Bing; Liu Zheng; Guo Xia-Sheng; Zhang Dong

    2011-01-01

    Microbubbles promise to enhance the efficiency of ultrasound-mediated drug delivery and gene therapy by taking advantage of artificial cavitation nuclei. The purpose of this study is to examine the ultrasound-induced hemolysis in the application of drug delivery in the presence of microbubbles. To achieve this goal, human red blood cells mixed with microbubbles were exposed to 1-MHz pulsed ultrasound. The hemolysis level was measured by a flow cytometry, and the cavitation dose was detected by a passive cavitation detecting system. The results demonstrate that larger cavitation dose would be generated with the increase of acoustic pressure, which might give rise to the enhancement of hemolysis. Besides the experimental observations, the acoustic pressure dependence of the radial oscillation of microbubble was theoretically estimated. The comparison between the experimental and calculation results indicates that the hemolysis should be highly correlated to the acoustic cavitation.

  7. Quantifying of the Thermal Dynamic Characteristics of the Combustion System for Underground Coal Fire and its Impact on Environment in Xinjiang region, China

    Science.gov (United States)

    ZENG, Qiang; Tiyip, Tashpolat; Wuttke, Manfred; NIE, Jing; PU, Yan

    2015-04-01

    Underground Coal fire (UCF) is one disaster associated with coal mining activities around the world. The UCF not only burns up the coal reservoir, but also causes serious environmental problems, such as the pollution to air, the damage to soils, and the contamination to surface and underground water and consequently the health problem to human beings. In the present paper, the authors attempts to quantify the thermal dynamic characteristics of the combustion system for UCF and its impact on environment by modeling, including delineating the physical boundary of UCF zone, modeling of the capacity of the oxygen supply to UCF, modeling the intensity of heat generation from UCF and modeling the process of heat transfer within UCF and its surrounding environment. From this research, results were obtained as follows: First of all, based on the rock control theory, a model was proposed to depict the physical boundary of UCF zone which is important for coal fire research. Secondly, with analyzing the characteristics of air and smoke flow within UCF zone, an air/smoke flow model was proposed and consequently a method was put forward to calculate the capacity of oxygen supply to the UCF. Thirdly, with analyzing the characteristics of coal combustion within UCF zone, a method of calculating the intensity of heat generation from UCF, i.e., the heat source models, was established. Heat transfer with UCF zone includes the heat conductivity within UCF zone, the heat dissipation by radiation from the surface of fire zone, and the heat dissipation by convection as well as the heat loss taken away by mass transport. The authors also made an effort to depict the process of heat transfer by quantitative methods. Finally, an example of Shuixigou coal fire was given to illustrate parts of above models. Further more, UCF's impact on environment, such as the heavy metals contamination to surface soil of fire zone and the characteristics of gaseous pollutants emission from the UCF also was

  8. The dynamic process of atmospheric water sorption in [BMIM][Ac]: quantifying bulk versus surface sorption and utilizing atmospheric water as a structure probe.

    Science.gov (United States)

    Chen, Yu; Cao, Yuanyuan; Yan, Chuanyu; Zhang, Yuwei; Mu, Tiancheng

    2014-06-19

    The dynamic process of the atmospheric water absorbed in acetate-based ionic liquid 1-butyl-3-methyl-imidazolium acetate ([BMIM][Ac]) within 360 min could be described with three steps by using two-dimensional correlation infrared (IR) spectroscopy technique. In Step 1 (0-120 min), only bulk sorption via hydrogen bonding interaction occurs. In Step 2 (120-320 min), bulk and surface sorption takes place simultaneously via both hydrogen bonding interaction and van der Waals force. In Step 3, from 320 min to steady state, only surface sorption via van der Waals force occurs. Specifically, Step 2 could be divided into three substeps. Most bulk sorption with little surface sorption takes place in Step 2a (120-180 min), comparative bulk and surface sorption happens in Step 2b (180-260 min), and most surface sorption while little bulk sorption occurs in Step 2c (260-320 min). Interestingly, atmospheric water is found for the first time to be able to be used as a probe to detect the chemical structure of [BMIM][Ac]. Results show that one anion is surrounded by three C4,5H molecules and two anions are surrounded by five C2H molecules via hydrogen bonds, which are very susceptible to moisture water especially for the former one. The remaining five anions form a multimer (equilibrating with one dimer and one trimer) via a strong hydrogen bonding interaction, which is not easily affected by the introduction of atmospheric water. The alkyl of the [BMIM][Ac] cation aggregates to some extent by van der Walls force, which is moderately susceptible to the water attack. Furthermore, the proportion of bulk sorption vs surface sorption is quantified as about 70% and 30% within 320 min, 63% and 37% within 360 min, and 11% and 89% until steady-state, respectively.

  9. Optical steering of thermally generated microbubbles in a liquid for targeted metallic nanoparticle delivery

    Science.gov (United States)

    Krishnappa, Arjun; Abeywickrema, Ujitha; Banerjee, Partha

    2016-09-01

    A novel mathematical model is developed to investigate the behavior of thermally generated microbubbles in the presence of optical radiation to understand the mechanism of their steering. Forces acting on a bubble are studied in detail using a general force model. It has been proposed that these microbubbles with agglomerated metallic nanoparticles can be used for targeted drug delivery. The model can be extended to include the steering of bubbles with agglomerated silver or gold nanoparticles on their surface.

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

    Science.gov (United States)

    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.

  11. Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation.

    Science.gov (United States)

    McLaughlan, James; Ingram, Nicola; Smith, Peter R; Harput, Sevan; Coletta, P Louise; Evans, Stephen; Freear, Steven

    2013-12-01

    The therapeutic use of microbubbles for targeted drug or gene delivery is a highly active area of research. Phospholipid- encapsulated microbubbles typically have a polydisperse size distribution over the 1 to 10 μm range and can be functionalized for molecular targeting and loaded with drugcarrying liposomes. Sonoporation through the generation of shear stress on the cell membrane by microbubble oscillations is one mechanism that results in pore formation in the cell membrane and can improve drug delivery. A microbubble oscillating at its resonant frequency would generate maximum shear stress on a membrane. However, because of the polydisperse nature of phospholipid microbubbles, a range of resonant frequencies would exist in a single population. In this study, the use of linear chirp excitations was compared with equivalent duration and acoustic pressure tone excitations when measuring the sonoporation efficiency of targeted microbubbles on human colorectal cancer cells. A 3 to 7 MHz chirp had the greatest sonoporation efficiency of 26.9 ± 5.6%, compared with 16.4 ± 1.1% for the 1.32 to 3.08 MHz chirp. The equivalent 2.2- and 5-MHz tone excitations have efficiencies of 12.8 ± 2.1% and 15.6 ± 1.1%, respectively, which were all above the efficiency of 4.1 ± 3.1% from the control exposure.

  12. Doxorubicin liposome-loaded microbubbles for contrast imaging and ultrasound-triggered drug delivery.

    Science.gov (United States)

    Escoffre, Jean-Michel; Mannaris, Christophoros; Geers, Bart; Novell, Anthony; Lentacker, Ine; Averkiou, Michalakis; Bouakaz, Ayache

    2013-01-01

    Targeted drug delivery under image guidance is gaining more interest in the drug-delivery field. The use of microbubbles as contrast agents in diagnostic ultrasound provides new opportunities in noninvasive image-guided drug delivery. In the present study, the imaging and therapeutic properties of novel doxorubicin liposome-loaded microbubbles are evaluated. The results showed that at scanning settings (1.7 MHz and mechanical index 0.2), these microbubbles scatter sufficient signal for nonlinear ultrasound imaging and can thus be imaged in real time and be tracked in vivo. In vitro therapeutic evaluation showed that ultrasound at 1 MHz and pressures up to 600 kPa in combination with the doxorubicin liposomeloaded microbubbles induced 4-fold decrease of cell viability compared with treatment with free doxorubicin or doxorubicin liposome-loaded microbubbles alone. The therapeutic effectiveness is correlated to an ultrasound-triggered release of doxorubicin from the liposomes and an enhanced uptake of the free doxorubicin by glioblastoma cells. The results obtained demonstrate that the combination of ultrasound and the doxorubicin liposome-loaded microbubbles can provide a new method of noninvasive image-guided drug delivery.

  13. Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles.

    Science.gov (United States)

    Vandenbroucke, Roosmarijn E; Lentacker, Ine; Demeester, Joseph; De Smedt, Stefaan C; Sanders, Niek N

    2008-03-20

    Short interfering RNA (siRNA) attracts much attention for the treatment of various diseases. However, its delivery, especially via systemic routes, remains a challenge. Indeed, naked siRNAs are rapidly degraded, while complexed siRNAs massively aggregate in the blood or are captured by macrophages. Although this can be circumvented by PEGylation, we found that PEGylation had a strong negative effect on the gene silencing efficiency of siRNA-liposome complexes (siPlexes). Recently, ultrasound combined with microbubbles has been used to deliver naked siRNA but the gene silencing efficiency is rather low and very high amounts of siRNA are required. To overcome the negative effects of PEGylation and to enhance the efficiency of ultrasound assisted siRNA delivery, we coupled PEGylated siPlexes (PEG-siPlexes) to microbubbles. Ultrasound radiation of these microbubbles resulted in massive release of unaltered PEG-siPlexes. Interestingly, PEG-siPlexes loaded on microbubbles were able to enter cells after exposure to ultrasound, in contrast to free PEG-siPlexes, which were not able to enter cells rapidly. Furthermore, these PEG-siPlex loaded microbubbles induced, in the presence of ultrasound, much higher gene silencing than free PEG-siPlexes. Additionally, the PEG-siPlex loaded microbubbles only silenced the expression of genes in the presence of ultrasound, which allows space and time controlled gene silencing.

  14. Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle.

    Science.gov (United States)

    Kheirolomoom, Azadeh; Dayton, Paul A; Lum, Aaron F H; Little, Erika; Paoli, Eric E; Zheng, Hairong; Ferrara, Katherine W

    2007-04-23

    A new acoustically-active delivery vehicle was developed by conjugating liposomes and microbubbles, using the high affinity interaction between avidin and biotin. Binding between microbubbles and liposomes, each containing 5% DSPE-PEG2kBiotin, was highly dependent on avidin concentration and observed above an avidin concentration of 10 nM. With an optimized avidin and liposome concentration, we measured and calculated as high as 1000 to 10,000 liposomes with average diameters of 200 and 100 nm, respectively, attached to each microbubble. Replacing avidin with neutravidin resulted in 3-fold higher binding, approaching the calculated saturation level. High-speed photography of this new drug delivery vehicle demonstrated that the liposome-bearing microbubbles oscillate in response to an acoustic pulse in a manner similar to microbubble contrast agents. Additionally, microbubbles carrying liposomes could be spatially concentrated on a monolayer of PC-3 cells at the focal point of ultrasound beam. As a result of cell-vehicle contact, the liposomes fused with the cells and internalization of NBD-cholesterol occurred shortly after incubation at 37 degrees C, with internalization of NBD-cholesterol substantially enhanced in the acoustic focus.

  15. The influence of intercalating perfluorohexane into lipid shells on nano and microbubble stability.

    Science.gov (United States)

    Abou-Saleh, Radwa H; Peyman, Sally A; Johnson, Benjamin R G; Marston, Gemma; Ingram, Nicola; Bushby, Richard; Coletta, P Louise; Markham, Alexander F; Evans, Stephen D

    2016-09-14

    Microbubbles are potential diagnostic and therapeutic agents. In vivo stability is important as the bubbles are required to survive multiple passages through the heart and lungs to allow targeting and delivery. Here we have systematically varied key parameters affecting microbubble lifetime to significantly increase in vivo stability. Whilst shell and core composition are found to have an important role in improving microbubble stability, we show that inclusion of small quantities of C6F14 in the microbubble bolus significantly improves microbubble lifetime. Our results indicate that C6F14 inserts into the lipid shell, decreasing surface tension to 19 mN m(-1), and increasing shell resistance, in addition to saturating the surrounding medium. Surface area isotherms suggest that C6F14 incorporates into the acyl chain region of the lipid at a high molar ratio, indicating ∼2 perfluorocarbon molecules per 5 lipid molecules. The resulting microbubble boluses exhibit a higher in vivo image intensity compared to commercial compositions, as well as longer lifetimes.

  16. Microbubbles and Ultrasound: Therapeutic Applications in Diabetic Nephropathy.

    Science.gov (United States)

    Cao, Wei J; Matkar, Pratiek N; Chen, Hao H; Mofid, Azadeh; Leong-Poi, Howard

    2016-01-01

    Diabetic nephropathy (DN) remains one of the most common causes of end-stage renal disease. Current therapeutic strategies aiming at optimization of serum glucose and blood pressure are beneficial in early stage DN, but are unable to fully prevent disease progression. With the limitations of current medical therapies and the shortage of available donor organs for kidney transplantation, the need for novel therapies to address DN complications and prevent progression towards end-stage renal failure is crucial. The development of ultrasound technology for non-invasive and targeted in-vivo gene delivery using high power ultrasound and carrier microbubbles offers great therapeutic potential for the prevention and treatment of DN. The promising results from preclinical studies of ultrasound-mediated gene delivery (UMGD) in several DN animal models suggest that UMGD offers a unique, non-invasive platform for gene- and cell-based therapies targeted against DN with strong clinical translation potential.

  17. Particle migration and sorting in microbubble streaming flows

    Science.gov (United States)

    Thameem, Raqeeb; Hilgenfeldt, Sascha

    2016-01-01

    Ultrasonic driving of semicylindrical microbubbles generates strong streaming flows that are robust over a wide range of driving frequencies. We show that in microchannels, these streaming flow patterns can be combined with Poiseuille flows to achieve two distinctive, highly tunable methods for size-sensitive sorting and trapping of particles much smaller than the bubble itself. This method allows higher throughput than typical passive sorting techniques, since it does not require the inclusion of device features on the order of the particle size. We propose a simple mechanism, based on channel and flow geometry, which reliably describes and predicts the sorting behavior observed in experiment. It is also shown that an asymptotic theory that incorporates the device geometry and superimposed channel flow accurately models key flow features such as peak speeds and particle trajectories, provided it is appropriately modified to account for 3D effects caused by the axial confinement of the bubble. PMID:26958103

  18. Microvascular contrast enhancement in optical coherence tomography using microbubbles

    Science.gov (United States)

    Assadi, Homa; Demidov, Valentin; Karshafian, Raffi; Douplik, Alexandre; Vitkin, I. Alex

    2016-07-01

    Gas microbubbles (MBs) are investigated as intravascular optical coherence tomography (OCT) contrast agents. Agar + intralipid scattering tissue phantoms with two embedded microtubes were fabricated to model vascular blood flow. One was filled with human blood, and the other with a mixture of human blood + MB. Swept-source structural and speckle variance (sv) OCT images, as well as speckle decorrelation times, were evaluated under both no-flow and varying flow conditions. Faster decorrelation times and higher structural and svOCT image contrasts were detected in the presence of MB in all experiments. The effects were largest in the svOCT imaging mode, and uniformly diminished with increasing flow velocity. These findings suggest the feasibility of utilizing MB for tissue hemodynamic investigations and for microvasculature contrast enhancement in OCT angiography.

  19. Growth control of sessile microbubbles in PDMS devices

    CERN Document Server

    Volk, Andreas; Kähler, Christian J; Hilgenfeldt, Sascha; Marin, Alvaro

    2015-01-01

    In a microfluidic environment, the presence of bubbles is often detrimental to the functionality of the device, leading to clogging or cavitation, but microbubbles can also be an indispensable asset in other applications such as microstreaming. In either case, it is crucial to understand and control the growth or shrinkage of these bodies of air, in particular in common soft-lithography devices based on polydimethylsiloxane (PDMS), which is highly permeable to gases. In this work, we study the gas transport into and out of a bubble positioned in a microfluidic device, taking into account the direct gas exchange through PDMS as well as the transport of gas through the liquid in the device. Hydrostatic pressure regulation allows for the quantitative control of growth, shrinkage, or the attainment of a stable equilibrium bubble size. We find that the vapor pressure of the liquid plays an important role for the balance of gas transport, accounting for variability in experimental conditions and suggesting addition...

  20. Particle migration and sorting in microbubble streaming flows.

    Science.gov (United States)

    Thameem, Raqeeb; Rallabandi, Bhargav; Hilgenfeldt, Sascha

    2016-01-01

    Ultrasonic driving of semicylindrical microbubbles generates strong streaming flows that are robust over a wide range of driving frequencies. We show that in microchannels, these streaming flow patterns can be combined with Poiseuille flows to achieve two distinctive, highly tunable methods for size-sensitive sorting and trapping of particles much smaller than the bubble itself. This method allows higher throughput than typical passive sorting techniques, since it does not require the inclusion of device features on the order of the particle size. We propose a simple mechanism, based on channel and flow geometry, which reliably describes and predicts the sorting behavior observed in experiment. It is also shown that an asymptotic theory that incorporates the device geometry and superimposed channel flow accurately models key flow features such as peak speeds and particle trajectories, provided it is appropriately modified to account for 3D effects caused by the axial confinement of the bubble.

  1. Microbubbles loaded with nanoparticles: a route to multiple imaging modalities.

    Science.gov (United States)

    Park, Jai Il; Jagadeesan, Dinesh; Williams, Ross; Oakden, Wendy; Chung, Siyon; Stanisz, Greg J; Kumacheva, Eugenia

    2010-11-23

    We report a single-step approach to producing small and stable bubbles functionalized with nanoparticles. The strategy includes the following events occurring in sequence: (i) a microfluidic generation of bubbles from a mixture of CO(2) and a minute amount of gases with low solubility in water, in an aqueous solution of a protein, a polysaccharide, and anionic nanoparticles; (ii) rapid dissolution of CO(2) leading to the shrinkage of bubbles and an increase in acidity of the medium in the vicinity of the bubbles; and (iii) co-deposition of the biopolymers and nanoparticles at the bubble-liquid interface. The proposed approach yielded microbubbles with a narrow size distribution, long-term stability, and multiple functions originating from the attachment of metal oxide, metal, or semiconductor nanoparticles onto the bubble surface. We show the potential applications of these bubbles in ultrasound and magnetic resonance imaging.

  2. Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model

    Science.gov (United States)

    Bae, Yun Jung; Yoon, Young Il; Yoon, Tae-Jong

    2016-01-01

    Objective To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. Materials and Methods Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. Results Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). Conclusion Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo. PMID:27390541

  3. Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Yun Jung [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Yoon, Young Il [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 16229 (Korea, Republic of); Yoon, Tae-Jong [Department of Applied Bioscience, College of Life Science, CHA University, Pocheon 11160 (Korea, Republic of); College of Pharmacy, Ajou University, Suwon 16499 (Korea, Republic of); Lee, Hak Jong [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 16229 (Korea, Republic of)

    2016-11-01

    To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.

  4. Ultrasound-guided delivery of siRNA and a chemotherapeutic drug by using microbubble complexes: In vitro and in vivo evaluations in a prostate cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Yun Jung; Yoon, Young Il; Lee, Hak Jong [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yoon, Tae Jong [Dept. of Applied Bioscience, College of Life Science, CHA University, Pocheon (Korea, Republic of)

    2016-07-15

    To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.

  5. Controlled assembly of magnetic nanoparticles on microbubbles for multimodal imaging.

    Science.gov (United States)

    Duan, Lei; Yang, Fang; Song, Lina; Fang, Kun; Tian, Jilai; Liang, Yijun; Li, Mingxi; Xu, Ning; Chen, Zhongda; Zhang, Yu; Gu, Ning

    2015-07-21

    Magnetic microbubbles (MMBs) consisting of microbubbles (MBs) and magnetic nanoparticles (MNPs) were synthesized for use as novel markers for improving multifunctional biomedical imaging. The MMBs were fabricated by assembling MNPs in different concentrations on the surfaces of MBs. The relationships between the structure, magnetic properties, stability of the MMBs, and their use in magnetic resonance/ultrasound (MR/US) dual imaging applications were determined. The MNPs used were NPs of 3-aminopropyltriethoxysilane (APTS)-functionalized superparamagnetic iron oxide γ-Fe2O3 (SPIO). SPIO was assembled on the surfaces of polymer MBs using a "surface-coating" approach. An analysis of the underlying mechanism showed that the synergistic effects of covalent coupling, electrostatic adsorption, and aggregation of the MNPs allowed them to be unevenly assembled in large amounts on the surfaces of the MBs. With an increase in the MNP loading amount, the magnetic properties of the MMBs improved significantly; in this way, the shell structure and mechanical properties of the MMBs could be modified. For surface densities ranging from 2.45 × 10(-7) μg per MMB to 8.45 × 10(-7) μg per MMB, in vitro MR/US imaging experiments showed that, with an increase in the number of MNPs on the surfaces of the MBs, the MMBs exhibited better T2 MR imaging contrast, as well as an increase in the US contrast for longer durations. In vivo experiments also showed that, by optimizing the structure of the MMBs, enhanced MR/US dual-modality image signals could be obtained for mouse tumors. Therefore, by adjusting the shell composition of MBs through the assembly of MNPs in different concentrations, MMBs with good magnetic and acoustic properties for MR/US dual-modality imaging contrast agents could be obtained.

  6. Biodesulfurization of flue gases using synthesis gas delivered as microbubbles

    Energy Technology Data Exchange (ETDEWEB)

    Selvaraj, P.T.; Bredwell, M.D.; Little, M.H.; Kaufman, E.N. [Oak Ridge National Lab., TN (United States). Bioprocessing Research and Development Center

    1997-03-01

    In this study, the authors have focused research on utilizing a gas mixture containing 36% H{sub 2}, 47% CO, 10% CO{sub 2}, 5% CH{sub 4} and a balance of N{sub 2} as a model coal synthesis gas as a low-cost feedstock for sulfate-reducing bacteria cultures. Coal synthesis gas will be readily available in power plants and the biological utilization of syn-gas as a carbon and energy source produces no organic end product that has to be processed prior to its disposal. Coal synthesis gas is, however, sparingly soluble in aqueous phase. This process utilizing SRB with syn-gas feedstock may be mass transfer limited and methods to enhance the mass transport have been investigated. A CSTR with cell recycle and a trickle bed reactor with cells immobilized in BIO-SEP{trademark} polymeric beads were operated with syn-gas feedstock to obtain maximum productivity for SO{sub 2} reduction to H{sub 2}S. The CSTR reactor was then fed with syn-gas as microbubbles in an effort to improve the mass transfer properties. With syn-gas fed as microbubbles, productivity in the CSTR increased from 1.2 to 2.1 mmol/h {center_dot} L in 33 h. This has been observed at the same biomass concentration of 5 g/L. This shows the mass transport limitation in the above process. In the trickle bed reactor, maximum productivity of 8.8 mmol/h {center_dot} L was achieved with less carbon and energy requirements (1 mol H{sub 2} and 1.2 mol CO per mol of SO{sub 2}) indicating better surface to volume ratio with cells immobilized in the pores of polymeric beads.

  7. Nanoparticle coated optical fibers for single microbubble generation

    Science.gov (United States)

    Pimentel-Domínguez, Reinher; Hernández-Cordero, Juan

    2011-09-01

    The study of bubbles and bubbly flows is important in various fields such as physics, chemistry, medicine, geophysics, and even the food industry. A wide variety of mechanical and acoustic techniques have been reported for bubble generation. Although a single bubble may be generated with these techniques, controlling the size and the mean lifetime of the bubble remains a difficult task. Most of the optical methods for generation of microbubbles involve high-power pulsed laser sources focused in absorbing media such as liquids or particle solutions. With these techniques, single micron-sized bubbles can be generated with typical mean lifetimes ranging from nano to microseconds. The main problem with these bubbles is their abrupt implosion: this produces a shock wave that can potentially produce damages on the surroundings. These effects have to be carefully controlled in biological applications and in laser surgery, but thus far, not many options are available to effectively control micron-size bubble growth. In this paper, we present a new technique to generate microbubbles in non-absorbing liquids. In contrast to previous reports, the proposed technique uses low-power and a CW radiation from a laser diode. The laser light is guided through an optical fiber whose output end has been coated with nanostructures. Upon immersing the tip of the fiber in ethanol or water, micron-size bubbles can be readily generated. With this technique, bubble growth can be controlled through adjustments on the laser power. We have obtained micron-sized bubbles with mean lifetimes in the range of seconds. Furthermore, the generated bubbles do not implode, as verified with a high-speed camera and flow visualization techniques.

  8. Modeling the interaction of microbubbles: Effects of proximity, confinement, and excitation amplitude

    Science.gov (United States)

    Wiedemair, W.; Tukovic, Z.; Jasak, H.; Poulikakos, D.; Kurtcuoglu, V.

    2014-06-01

    The interaction of closely spaced microbubbles (MBs) exposed to a transient external pressure field is relevant for a variety of industrial and medical applications. We present a computational framework employing an interface tracking approach to model the transient dynamics of multiple, interacting, insonated MBs in arbitrary settings. In particular, this technique allows studying the effects of mutual proximity, confinement, and variations in excitation amplitude on the translatory motion of pairs of differently sized MBs. Domains of mutual repulsion or attraction are observed for closely spaced MBs in the investigated range of excitation frequencies. The repulsion domain widens and shifts to lower frequencies with increasing excitation pressure amplitude. When the MBs are confined in rigid tubes of decreasing diameters, we observe a shift of the translatory patterns towards lower frequencies, accompanied by a change in relative strength of the two translation modes. This effect is correlated to a decrease of the resonance frequency due to confinement which causes changes in oscillation amplitude and phase shift between the bubble vibrations. Coupling to the viscous host liquid gives rise to phenomena such as collective MB drift, non-symmetric attraction or repulsion, and reversal of translation direction. A system comprising six MBs inside a narrow tube highlights the potential of the computational framework to treat complex setups with multiple bubbles.

  9. 3-D In Vitro Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles.

    Science.gov (United States)

    Christensen-Jeffries, Kirsten; Brown, Jemma; Aljabar, Paul; Tang, Mengxing; Dunsby, Christopher; Eckersley, Robert J

    2017-07-31

    Standard clinical ultrasound (US) imaging frequencies are unable to resolve microvascular structures due to the fundamental diffraction limit of US waves. Recent demonstrations of 2D super-resolution both in vitro and in vivo have demonstrated that fine vascular structures can be visualized using acoustic single bubble localization. Visualization of more complex and disordered 3D vasculature, such as that of a tumor, requires an acquisition strategy which can additionally localize bubbles in the elevational plane with high precision in order to generate super-resolution in all three dimensions. Furthermore, a particular challenge lies in the need to provide this level of visualization with minimal acquisition time. In this work, we develop a fast, coherent US imaging tool for microbubble localization in 3D using a pair of US transducers positioned at 90°. This allowed detection of point scatterer signals in 3 dimensions with average precisions equal to 1.9 µm in axial and elevational planes, and 11 µm in the lateral plane, compared to the diffraction limited point spread function full widths at half maximum of 488 µm, 1188 µm and 953 µm of the original imaging system with a single transducer. Visualization and velocity mapping of 3D in vitro structures was demonstrated far beyond the diffraction limit. The capability to measure the complete flow pattern of blood vessels associated with disease at depth would ultimately enable analysis of in vivo microvascular morphology, blood flow dynamics and occlusions resulting from disease states.

  10. Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

    Directory of Open Access Journals (Sweden)

    Barrefelt A

    2013-08-01

    Full Text Available Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 2Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 4Division of Functional Materials, Department of Materials and Nano Physics, Royal Institute of Technology, Stockholm, Sweden; 5Surflay Nanotec GmbH, Berlin, Germany; 6Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden *These authors contributed equally to this work Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol (PVA microbubbles containing superparamagnetic iron oxide (SPION trapped between the PVA layers (SPION microbubbles. Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from

  11. Quantifying the adaptive cycle

    Science.gov (United States)

    Angeler, David G.; Allen, Craig R.; Garmestani, Ahjond S.; Gunderson, Lance H.; Hjerne, Olle; Winder, Monika

    2015-01-01

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.

  12. Advanced treatment of acrylic fiber manufacturing wastewater with a combined microbubble-ozonation/ultraviolet irradiation process

    KAUST Repository

    Zheng, Tianlong

    2015-01-01

    This work investigated the effectiveness of a combination of microbubble-ozonation and ultraviolet (UV) irradiation for the treatment of secondary wastewater effluent of a wet-spun acrylic fiber manufacturing plant. Under reactor condition (ozone dosage of 48 mg L-1, UV fluence rate of 90 mW cm-2, initial pH of 8.0, and reaction time of 120 min), the biodegradability (represented as BOD5/CODcr) of the wastewater improved from 0.18 to 0.47. This improvement in biodegradability is related to the degradation of alkanes, aromatic compounds, and other bio-refractory organic compounds. The combination of microbubble-ozonation and UV irradiation synergistically improved treatment efficiencies by 228%, 29%, and 142% for CODcr, UV254 removal and BOD5/CODcr respectively after 120 min reaction time, as compared with the sum efficiency of microbubble-ozonation alone and UV irradiation alone. Hydroxyl radical production in the microbubble-ozonation/UV process was about 1.8 times higher than the sum production in microbubble-ozonation alone and UV irradiation alone. The ozone decomposition rate in the combined process was about 4.1 times higher than that in microbubble-ozonation alone. The microbubble-ozonation/UV process could be a promising technique for the treatment of bio-refractory organics in the acrylic fiber manufacturing industry. © 2015 Royal Society of Chemistry.

  13. Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization.

    Science.gov (United States)

    Farook, U; Stride, E; Edirisinghe, M J

    2009-03-01

    The use of phospholipid-coated microbubbles for medical applications is gaining considerable attention. However, the preparation of lipid-coated microbubble suspensions containing the ideal size and size distribution of bubbles still represents a considerable challenge. The most commonly used preparation methods of sonication and mechanical agitation result in the generation of polydisperse microbubbles with diameters ranging from less than 1 microm to greater than 50 microm. Efforts have been made via distinctly different techniques such as microfluidic and electrohydrodynamic bubbling to prepare lipid-coated microbubbles with diameters less than 10 microm and with a narrow size distribution, and recent results have been highly promising. In this paper, we describe a detailed investigation of the latter method that essentially combines liquid and air flow, and an applied electric field to generate microbubbles. A parametric plot was constructed between the air flow rate (Qg) and the lipid suspension flow rate (Ql) to identify suitable flow rate regimes for the preparation of phospholipid-coated microbubbles with a mean diameter of 6.6 microm and a standard deviation of 2.5 microm. The parametric plot has also helped in developing a scaling equation between the bubble diameter and the ratio Qg/Ql. At ambient temperature (22 degrees C), these bubbles were very stable with their size remaining almost unchanged for 160 min. The influence of higher temperatures such as the human body temperature (37 degrees C) on the size and stability of the microbubbles was also explored. It was found that the mean bubble diameter fell rapidly to begin with but then stabilized at 1-2 microm after 20 min.

  14. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved.

    Science.gov (United States)

    Lentacker, Ine; Geers, Bart; Demeester, Joseph; De Smedt, Stefaan C; Sanders, Niek N

    2010-01-01

    Drug delivery with microbubbles and ultrasound is gaining more and more attention in the drug delivery field due to its noninvasiveness, local applicability, and proven safety in ultrasonic imaging techniques. In this article, we tried to improve the cytotoxicity of doxorubicin (DOX)-containing liposomes by preparing DOX-liposome-containing microbubbles for drug delivery with therapeutic ultrasound. In this way, the DOX release and uptake can be restricted to ultrasound-treated areas. Compared to DOX-liposomes, DOX-loaded microbubbles killed at least two times more melanoma cells after exposure to ultrasound. After treatment of the melanoma cells with DOX-liposome-loaded microbubbles and ultrasound, DOX was mainly present in the nuclei of the cancer cells, whereas it was mainly detected in the cytoplasm of cells treated with DOX-liposomes. Exposure of cells to DOX-liposome-loaded microbubbles and ultrasound caused an almost instantaneous cellular entry of the DOX. At least two mechanisms were identified that explain the fast uptake of DOX and the superior cell killing of DOX-liposome-loaded microbubbles and ultrasound. First, exposure of DOX-liposome-loaded microbubbles to ultrasound results in the release of free DOX that is more cytotoxic than DOX-liposomes. Second, the cellular entry of the released DOX is facilitated due to sonoporation of the cell membranes. The in vitro results shown in this article indicate that DOX-liposome-loaded microbubbles could be a very interesting tool to obtain an efficient ultrasound-controlled DOX delivery in vivo.

  15. Optimization of transfection parameters for ultrasound/SonoVue microbubble-mediated hAng-1 gene delivery in vitro.

    Science.gov (United States)

    Zhou, Qing; Chen, Jin-Ling; Chen, Qian; Wang, Xiao; Deng, Qing; Hu, Bo; Guo, Rui-Qiang

    2012-12-01

    This study aimed to explore the effects of microbubble concentration, gene dosage, cell-microbubble mixing mode and fetal bovine serum (FBS) on gene delivery. 293T cells were transfected with Sonovue microbubbles carrying the hAng-1 gene via ultrasound irradiation. Various ultrasound exposure parameters and microbubble and DNA concentrations were investigated. In addition, FBS and the cell suspension or adherent mode was explored. Transfection efficiency and cell viability were used to determine the optimal transfection parameters. hAng-1 gene transfection efficiency gradually increased with elongation of ultrasound exposure and increasing microbubble concentration. However, if ultrasound irradiation exceeded 1.5 W/cm² and 30 sec or the microbubble concentration was over 20%, hAng-1 gene expression was significantly decreased, coupled with extensive cell death. Gene transfection levels were low under DNA concentrations less than 15 µg/ml. Furthermore, the gene transfer rate was significantly increased under cell suspension mode; FBS had no effect on hAng-1 gene transfection. The integrity of hAng-1 DNA was not affected by ultrasonic irradiation under optimal conditions. The optimal transfection parameters for the hAng-1 gene and Sonovue microbubble were ultrasound exposure of 1.5 W/cm² and 30 sec, 20% microbubbles, 15 µg/ml of DNA and under cell suspension mode.

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

    Science.gov (United States)

    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

  17. Transfection efficiency of TDL compound in HUVEC enhanced by ultrasound-targeted microbubble destruction.

    Science.gov (United States)

    Ren, Jian-Li; Wang, Zhi-Gang; Zhang, Yong; Zheng, Yuan-Yi; Li, Xing-Sheng; Zhang, Qun-Xia; Wang, Zhao-Xia; Xu, Chuan-Shan

    2008-11-01

    The aim of the present study was to explore the gene transfection efficiency of Tat peptide/plasmid DNA/ liposome (TDL) compound combined with ultrasound-targeted microbubble destruction (UTMD) in human umbilical vein endothelial cell (HUVEC). Tat peptide, plasmid DNA (pIRES2-EGFP-HGF) and Lipofectamine 2000 were used to prepare the TDL compound. Microbubbles were prepared using mechanic vibration. The expression of the report gene enhanced green fluorescent protein (EGFP) was observed using fluorescent microscopy and flow cytometry. The viability of HUVEC was measured by MTT assay. mRNA and protein of HGF was analyzed by reverse transcription-polymerase chain reaction and Western Blot. The intensity of green fluorescence and the gene transfection efficiency of TDL compound + microbubbles + ultrasound group were higher than those of other groups, and no significantly different viability was found between TDL compound + microbubbles + ultrasound group and the other groups. The HGF mRNA and HGF protein of TDL compound + microbubbles + ultrasound group were higher than those of other groups. Our finding demonstrated that UTMD could enhance the transfection efficiency of TDL compound without obvious effects on the cell viability of HUVEC, suggesting that the combination of UTMD and TDL compound might be a useful tool for the gene therapy of ischemic heart disease.

  18. Paclitaxel-liposome-microbubble complexes as ultrasound-triggered therapeutic drug delivery carriers.

    Science.gov (United States)

    Yan, Fei; Li, Lu; Deng, Zhiting; Jin, Qiaofeng; Chen, Juanjuan; Yang, Wei; Yeh, Chih-Kuang; Wu, Junru; Shandas, Robin; Liu, Xin; Zheng, Hairong

    2013-03-28

    Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered drug delivery to treat malignant tumors. However, the efficacy for ultrasound-assisted chemotherapy in vivo and the underlying mechanisms remain to be elucidated. Here, we investigated the feasibility of using paclitaxel-liposome-microbubble complexes (PLMC) as possible ultrasound (US)-triggered targeted chemotherapy against breast cancer. PTX-liposomes (PL) were conjugated to the microbubble (MB) surface through biotin-avidin linkage, increasing the drug-loading efficiency of MBs. The significant increased release of payloads from liposome-microbubble complexes was achieved upon US exposure. We used fluorescent quantum dots (QDs) as a model drug to show that released QDs were taken up by 4T1 breast cancer cells treated with QD-liposome-microbubble complexes (QLMC) and US, and uptake depended on the exposure time and intensity of insonication. We found that PLMC plus US inhibited tumor growth more effectively than PL plus US or PLMC without US, not only in vitro, but also in vivo. Histologically, the inhibition of tumor growth appeared to result from increased apoptosis and reduced angiogenesis in tumor xenografts. In addition, a significant increase of drug concentration in tumors was observed in comparison to treatment with non-conjugated PL or PLMC without US. The significant increase in an antitumor efficacy of PLMC plus US suggests their potential use as a new targeted US chemotherapeutic approach to inhibit breast cancer growth.

  19. Cellular characterization of ultrasound-stimulated microbubble radiation enhancement in a prostate cancer xenograft model

    Directory of Open Access Journals (Sweden)

    Azza A. Al-Mahrouki

    2014-03-01

    Full Text Available Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in a prostate cancer xenograft model in mice. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment, which consisted of radiation treatments alone (2 Gy or 8 Gy or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL revealed increased cell death within tumors exposed to combined treatments compared with untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67, blood leakage (factor VIII, angiogenesis (cluster of differentiation molecule CD31, ceramide-formation, angiogenesis signaling [vascular endothelial growth factor (VEGF], oxygen limitation (prolyl hydroxylase PHD2 and DNA damage/repair (γH2AX. Results demonstrated reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach could be a feasible option as a novel enhancing approach in radiation therapy.

  20. High Q silica microbubble resonators fabricated by heating a pressurized glass capillary

    Science.gov (United States)

    Yu, Zhe; Liu, Tiegen; Jiang, Junfeng; Liu, Kun; Chen, Wenjie; Zhang, Xuezhi; Lin, Xujun; Liu, Wenhui

    2014-11-01

    Microbubble resonators combine the unique properties of whispering gallery mode resonators with the capability of integrated microfluidics. The microbubble resonator is fabricated by heating the tapered tip of a pressurized glass capillary with oxyhydrogen flame. Firstly, a microtube with a diameter of 250um is stretched under heating of oxyhydrogen flame, the heating zone length is set to be 20mm and the length of stretch is set to be 7000um.Then nitrogen will be pumped in to the tapered microtube with the pressure of 0.1Mpa, the tapered tip will be heated by the oxyhydrogen flame continuously until a microbubble forms. An optical fiber taper with a diameter of 2 um, fabricated by stretching a single-mode optical fiber under flame was brought in contact with the microbubble to couple the light from a 1550nm tunable diode laser into the whispering gallery mode. The microbubble resonator has a Q factors up to 1.5 × 107 around 1550nm. Different concentrations of ethanol solution (from 5% to 30%) are filled into it in order to test the refractive index sensing capabilities of such resonator, which shows a sensitivity of 82nm/RIU.

  1. Endothelial Adhesion of Targeted Microbubbles in Both Small and Great Vessels Using Ultrasound Radiation Force

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2012-01-01

    Full Text Available The effectiveness of microbubble-mediated ultrasound molecular imaging and drug delivery has been significantly affected by the axial laminar flow of vessels which prevents ultrasound contrast agents (UCAs from targeting vascular endothelium. Studies show that acoustic manipulation could increase targeted UCA adhesion in microcirculation and some small vessels. In this study we demonstrate that ultrasound radiation force (USRF can also significantly enhance the targeted adhesion of microbubbles in both small and great vessels. Our results indicate that the UCA adhesion targeted to ICAM-1 expressed on mouse cremaster microvascular endothelial cells increase about 9-fold when USRF is applied at 1 MHz and 73.9 kPa. The adhesion of anti-CD34 microbubbles to the endothelia of rat abdominal aorta was visually analyzed using scanning electron microscopy for the first time and thousands of microbubbles were found attached to the aortic endothelia after USRF application at the same acoustic parameters. Our data illustrate that targeted adhesion of anti-CD34 microbubbles is possible in normal abdominal aorta and we demonstrate the potential of using USRF in molecular imaging of a vascular target.

  2. Performance of a fixed-bed biofilm reactor with microbubble aeration in aerobic wastewater treatment.

    Science.gov (United States)

    Zhang, Lei; Liu, Junliang; Liu, Chun; Zhang, Jing; Yang, Jingliang

    2016-01-01

    Microbubble aeration is supposed to be highly efficient for oxygen supply in aerobic wastewater treatment. In the present study, the performance of a fixed-bed biofilm reactor microbubble-aerated using a Shirasu porous glass (SPG) membrane system was investigated when treating synthetic municipal wastewater. The biofilm formation on the carriers was enhanced with microbubble aeration due to the strong adhesion of microbubbles to the solid surface. The dissolved oxygen concentration, the removals of chemical oxygen demand (COD) and nitrogen, and the oxygen utilization efficiency were influenced by the organic loading rate at a certain oxygen supply capacity. The relatively optimal organic loading rate was determined as 0.82 kgCOD/(m(3)d) when the oxygen supply capacity was 0.93 kgO(2)/(m(3)d), where COD and ammonia removal efficiencies were 91.7% and 53.9%, respectively. The corresponding SPG membrane area-based COD removal capacity was 6.88 kgCOD/(m(2)d). The oxygen utilization efficiency of microbubble aeration was obviously higher compared to conventional bubble aeration. The simultaneous nitrification and denitrification occurred in the biofilm reactor and the total nitrogen removal efficiency of 50.4% was achieved under these conditions. In addition, the increase in air supply capacity of the SPG membrane system was suggested to improve its energy utilization efficiency.

  3. Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction.

    Science.gov (United States)

    Borden, Mark A; Kruse, Dustin E; Caskey, Charles F; Zhao, Shukui; Dayton, Paul A; Ferrara, Katherine W

    2005-11-01

    We present the first study of the effects of monolayer shell physicochemical properties on the destruction of lipid-coated microbubbles during insonification with single, one-cycle pulses at 2.25 MHz and low-duty cycles. Shell cohesiveness was changed by varying phospholipid and emulsifier composition, and shell microstructure was controlled by postproduction processing. Individual microbubbles with initial resting diameters between 1 and 10 microm were isolated and recorded during pulsing with bright-field and fluorescence video microscopy. Microbubble destruction occurred through two modes: acoustic dissolution at 400 and 600 kPa and fragmentation at 800 kPa peak negative pressure. Lipid composition significantly impacted the acoustic dissolution rate, fragmentation propensity, and mechanism of excess lipid shedding. Less cohesive shells resulted in micron-scale or smaller particles of excess lipid material that shed either spontaneously or on the next pulse. Conversely, more cohesive shells resulted in the buildup of shell-associated lipid strands and globular aggregates of several microns in size; the latter showed a significant increase in total shell surface area and lability. Lipid-coated microbubbles were observed to reach a stable size over many pulses at intermediate acoustic pressures. Observations of shell microstructure between pulses allowed interpretation of the state of the shell during oscillation. We briefly discuss the implications of these results for therapeutic and diagnostic applications involving lipid-coated microbubbles as ultrasound contrast agents and drug/gene delivery vehicles.

  4. Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.

    Science.gov (United States)

    Gauthier, Marianne; Yin, Qian; Cheng, Jianjun; O'Brien, William D

    2015-08-01

    A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB. © 2015 by the American Institute of Ultrasound in Medicine.

  5. Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.

    Directory of Open Access Journals (Sweden)

    Yu-Ren Liou

    Full Text Available Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs conjugated with antibodies (i.e., targeted biotin-MBs. Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs, which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+ and MDA-MB-453 cells (CD44-, which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+ is a commonly used cancer

  6. The breakup of intravascular microbubbles and its impact on the endothelium.

    Science.gov (United States)

    Wiedemair, Wolfgang; Tukovic, Zeljko; Jasak, Hrvoje; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2016-10-12

    Encapsulated microbubbles (MBs) serve as endovascular agents in a wide range of medical ultrasound applications. The oscillatory response of these agents to ultrasonic excitation is determined by MB size, gas content, viscoelastic shell properties and geometrical constraints. The viscoelastic parameters of the MB capsule vary during an oscillation cycle and change irreversibly upon shell rupture. The latter results in marked stress changes on the endothelium of capillary blood vessels due to altered MB dynamics. Mechanical effects on microvessels are crucial for safety and efficacy in applications such as focused ultrasound-mediated blood-brain barrier (BBB) opening. Since direct in vivo quantification of vascular stresses is currently not achievable, computational modelling has established itself as an alternative. We have developed a novel computational framework combining fluid-structure coupling and interface tracking to model the nonlinear dynamics of an encapsulated MB in constrained environments. This framework is used to investigate the mechanical stresses at the endothelium resulting from MB shell rupture in three microvessel setups of increasing levels of geometric detail. All configurations predict substantial elevation of up to 150 % for peak wall shear stress upon MB breakup, whereas global peak transmural pressure levels remain unaltered. The presence of red blood cells causes confinement of pressure and shear gradients to the proximity of the MB, and the introduction of endothelial texture creates local modulations of shear stress levels. With regard to safety assessments, the mechanical impact of MB breakup is shown to be more important than taking into account individual red blood cells and endothelial texture. The latter two may prove to be relevant to the actual, complex process of BBB opening induced by MB oscillations.

  7. New doxorubicin-loaded phospholipid microbubbles for targeted tumor therapy: Part I--Formulation development and in-vitro characterization.

    Science.gov (United States)

    Tinkov, Steliyan; Winter, Gerhard; Coester, Conrad; Bekeredjian, Raffi

    2010-04-01

    Despite high antitumor efficacy and a broad application spectrum, clinical treatment with anthracycline chemotherapeutics is often limited by severe adverse effects such as cardiotoxicity and myelosupression. In recent years, tumor drug targeting has evolved as a promising strategy to increase local drug concentration and reduce systemic side effects. One recent approach for targeting solid tumors is the application of microbubbles, loaded with chemotherapeutic drugs. These advanced drug carriers can be safely administered to the patient by intravenous infusion, and will circulate through the entire vasculature. Their drug load can be locally released by ultrasound targeted microbubble destruction. In addition, tumors can be precisely localized by diagnostic ultrasound since microbubbles act as contrast agents. In the present work a novel microbubble carrier for doxorubicin has been developed and characterized in-vitro. In contrast to many recent tumor-targeting MB designs the newly developed doxorubicin-loaded microbubbles possess a soft but stable phospholipid monolayer shell. Importantly, the active drug is embedded in the microbubble shell and is complexed to the phospholipids by both electrostatic and hydrophobic interactions. Despite their drug load, these novel microbubbles retained all important physical characteristics for ultrasound targeted microbubble destruction, comparable with the commercially available ultrasound contrast agents. In cell culture studies doxorubicin-loaded microbubbles in combination with ultrasound demonstrated an about 3 fold increase of the anti-proliferative activity compared to free doxorubicin and doxorubicin-loaded liposomes. For the first time in the literature the intracellular partition of free doxorubicin and phospholipid-complexed doxorubicin were compared. In conclusion, new doxorubicin-loaded microbubbles with ideal physical characteristics were developed. In-vitro studies show enhanced cytotoxic activity compared to

  8. Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation.

    Science.gov (United States)

    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.

  9. One-step microencapulation of nanoparticles and perfluorocarbon in microbubbles for potential application in controlled activation

    Science.gov (United States)

    Li, Guangbin; Si, Ting; Luo, Xisheng; Xu, Ronald

    2014-02-01

    Silver nanoparticles and perfluorocarbon are encapsulated in multilayered lipid microbubbles by a coaxial electro-flow focusing process. The process is characterized as a coaxial liquid jet in the core of a high-speed coflowing gas stream under an axial electric field. Different flow modes are identified and the stable cone-jet structure is formed in a wide range of process parameters. Core-shell structures of microbubbles with nanoparticles inside the shell are clearly observed. The effects of the main process parameters on the process outcome are studied systemically for the enhanced microbubble morphology. The preliminary elevation of the temperature in silver nanoparticle suspended perfluorcarbon is observed upon exposure to broadband light illumination, indicating the technical potential for light-activated drug delivery.

  10. Ultrasound mediated destruction of multifunctional microbubbles for image guided delivery of oxygen and drugs.

    Science.gov (United States)

    Chang, Shufang; Si, Ting; Zhang, Shiwu; Merrick, Mark A; Cohn, David E; Xu, Ronald X

    2016-01-01

    We synthesized multifunctional activatible microbubbles (MAMs) for ultrasound mediated delivery of oxygen and drugs with both ultrasound and fluorescence imaging guidance. Oxygen enriched perfluorocarbon (PFC) compound was encapsulated in liposome microbubbles (MBs) by a modified emulsification process. DiI dye was loaded as a model drug. The ultrasound targeted microbubble destruction (UTMD) process was guided by both ultrasonography and fluorescence imaging modalities. The process was validated in both a dialysis membrane tube model and a porcine carotid artery model. Our experiment results show that the UTMD process effectively facilitates the controlled delivery of oxygen and drug at the disease site and that the MAM agent enables ultrasound and fluorescence imaging guidance of the UTMD process. The proposed MAM agent can be potentially used for UTMD-mediated combination therapy in hypoxic ovarian cancer.

  11. An ultrahigh sensitivity, high resolution, aerostatic pressure sensor using microbubble resonators

    CERN Document Server

    Yang, Yong; Ward, Jonathan M; Chormaic, Síle Nic

    2016-01-01

    Sensors based on whispering gallery resonators can push achievable sensitivities and resolutions to their limits, while maintaining minute footprints. Here, we report on the fabrication of a microbubble resonator using two CO$_2$ beams focused on a microcapillary; the resulting microbubble has an ultrathin wall. We show that, even when the wall is as thin as 500 nm, an intrinsic quality factor of $10^7$ is achievable at the telecommunications C-band. Considering strain and stress of the material, we investigate the feasibility of using the microbubble as an aerostatic pressure sensor. The measured sensitivity is 19 GHz/bar and is at the limit of current techniques. We have found that the sensitivity can be improved to 38 GHz/bar at the 780 nm wavelength range, where the resolution for pressure sensing is 0.14 mbar and the Q-factor remains higher than $10^7$.

  12. Effects of ambient pressure on the subharmonic response from encapsulated microbubbles

    CERN Document Server

    Mobadersany, Nima; Sarkar, Kausik

    2015-01-01

    Subharmonic response from contrast microbubbles as a function of ambient overpressure is numerically investigated for subharmonic aided noninvasive estimation of local organ level blood pressure. Three different interfacial rheological models for the encapsulation is used with material parameters appropriate for a common lipid coated contrast agent Sonazoid. The subharmonic response is seen to either decrease, increase or vary nonmonotonically with increasing ambient pressure. Compared to a free microbubbles important differences arise due to the encapsulation. Specifically due to the enhanced damping due to encapsulation, the range of excitation over which subharmonic is seen is broader than that in free microbubbles. This results in different trends of subharmonic response at the same excitation frequency for different excitation pressures. The observed behaviors are explained by investigating subharmonic generation threshold and resonance frequency.

  13. Micro-bubble morphologies following drop impacts onto a pool surface

    KAUST Repository

    Thoroddsen, Sigurdur T.

    2012-10-01

    When a drop impacts at low velocity onto a pool surface, a hemispheric air layer cushions and can delay direct contact. Herein we use ultra-high-speed video to study the rupture of this layer, to explain the resulting variety of observed distribution of bubbles. The size and distribution of micro-bubbles is determined by the number and location of the primary punctures. Isolated holes lead to the formation of bubble necklaces when the edges of two growing holes meet, whereas bubble nets are produced by regular shedding of micro-bubbles from a sawtooth edge instability. For the most viscous liquids the air film contracts more rapidly than the capillary-viscous velocity through repeated spontaneous ruptures of the edge. From the speed of hole opening and the total volume of micro-bubbles we conclude that the air sheet ruptures when its thickness approaches ?100.

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

    Science.gov (United States)

    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.

  15. Growth control of sessile microbubbles in PDMS devices.

    Science.gov (United States)

    Volk, Andreas; Rossi, Massimiliano; Kähler, Christian J; Hilgenfeldt, Sascha; Marin, Alvaro

    2015-12-21

    In a microfluidic environment, the presence of bubbles is often detrimental to the functionality of the device, leading to clogging or cavitation, but microbubbles can also be an indispensable asset in other applications such as microstreaming. In either case, it is crucial to understand and control the growth or shrinkage of these bodies of air, in particular in common soft-lithography devices based on polydimethylsiloxane (PDMS), which is highly permeable to gases. In this work, we study the gas transport into and out of a bubble positioned in a microfluidic device, taking into account the direct gas exchange through PDMS as well as the transport of gas through the liquid in the device. Hydrostatic pressure regulation allows for the quantitative control of growth, shrinkage, or the attainment of a stable equilibrium bubble size. We find that the vapor pressure of the liquid plays an important role for the balance of gas transport, accounting for variability in experimental conditions and suggesting additional means of bubble size control in applications.

  16. Excitation threshold for subharmonic generation from contrast microbubbles.

    Science.gov (United States)

    Katiyar, Amit; Sarkar, Kausik

    2011-11-01

    Six models of contrast microbubbles are investigated to determine the excitation threshold for subharmonic generation. The models are applied to a commercial contrast agent; its characteristic parameters according to each model are determined using experimentally measured ultrasound attenuation. In contrast to the classical perturbative result, the minimum threshold for subharmonic generation is not always predicted at excitation with twice the resonance frequency; instead it occurs over a range of frequencies from resonance to twice the resonance frequency. The quantitative variation of the threshold with frequency depends on the model and the bubble radius. All models are transformed into a common interfacial rheological form, where the encapsulation is represented by two radius dependent surface properties-effective surface tension and surface dilatational viscosity. Variation of the effective surface tension with radius, specifically having an upper limit (resulting from strain softening or rupture of the encapsulation during expansion), plays a critical role. Without the upper limit, the predicted threshold is extremely large, especially near the resonance frequency. Having a lower limit on surface tension (e.g., zero surface tension in the buckled state) increases the threshold value at twice the resonance frequency, in some cases shifting the minimum threshold toward resonance.

  17. Polymeric microbubbles as delivery vehicles for sensitizers in sonodynamic therapy.

    Science.gov (United States)

    McEwan, Conor; Fowley, Colin; Nomikou, Nikolitsa; McCaughan, Bridgeen; McHale, Anthony P; Callan, John F

    2014-12-16

    Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitizer drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitizer drugs to their surface results in a significant reduction in particle stability. In this Article, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumors (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumor volume by 34% 4 days after treatment while tumors treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitizers in SDT.

  18. Stability analysis of an encapsulated microbubble against gas diffusion.

    Science.gov (United States)

    Katiyar, Amit; Sarkar, Kausik

    2010-03-01

    Linear stability analysis is performed for a mathematical model of diffusion of gases from an encapsulated microbubble. It is an Epstein-Plesset model modified to account for encapsulation elasticity and finite gas permeability. Although bubbles, containing gases other than air, are considered, the final stable bubble, if any, contains only air, and stability is achieved only when the surrounding medium is saturated or oversaturated with air. In absence of encapsulation elasticity, only a neutral stability is achieved for zero surface tension, the other solution being unstable. For an elastic encapsulation, different equilibrium solutions are obtained depending on the saturation level and whether the surface tension is smaller or higher than the elasticity. For an elastic encapsulation, elasticity can stabilize the bubble. However, imposing a non-negativity condition on the effective surface tension (consisting of reference surface tension and the elastic stress) leads to an equilibrium radius which is only neutrally stable. If the encapsulation can support a net compressive stress, it achieves actual stability. The linear stability results are consistent with our recent numerical findings. Physical mechanisms for the stability or instability of various equilibriums are provided.

  19. 微泡对气体交换影响的理论研究%The Theoretical Study for the Gas Exchange of Microbubbles at Different Positions

    Institute of Scientific and Technical Information of China (English)

    周翔; 柳晓军; 李珂; 庄华; 罗燕; 彭玉兰; 解慧琪

    2012-01-01

    Microbubbles have been used in ultrasound contrast imaging for over 10 years. However,influence of microbubbles for gas exchange is still difficult to know. The modelling of the gas exchange procedures between microbubble and tissue is further complicated because of incomplete understanding of the processes that determine bubble formation. Therefore,the authors introduced a new model for describing the exchange of inert gas between tissues and blood based on distributed capillary units or lumped compartments,either of which may be perfusion- or diffusion-limited. According to the Fick theory,Boyle law and Dalton law,the mathematical model for gas exchange in micorobubble was made. Three different positions for gas exchange at normal condition and high oxygen pressure were simulated by Matlab5.0. The theory results indicate that for normal condition,O2,CO2 and N2 have the similar dynamic process at different positions. For high O2 pressure condition,high O2 volume was carried to tissue by micorobubble,and large volume of microbubble plus high O2 pressure may produce available local gas physiological effects.%依据菲克第一定律、玻意耳定律及道尔顿气体分压定律,建立微泡内外气体交换的数学模型.通过理论推导和计算机模拟,研究微泡在不同条件下对机体的肺部、动脉系统及其周围组织等不同部位微循环中气体交换的影响.理论分析结果显示,O2、CO2及N2在三个部位都呈现为由内向外的弥散过程,且在正常呼吸条件下,超声造影剂微泡不会对周围组织微循环的气体交换产生有效的生理作用.而在吸氧35%或70%的条件下,微泡的携氧量明显增加,对三个部位局部周围组织微循环的气体交换产生一定影响.

  20. Study of interactions between cells and microbubbles in high speed centrifugation field for biomolecule delivery.

    Science.gov (United States)

    He, Chuan; Chen, Jie

    2014-01-01

    Biomolecule delivery has a very wide range of applications in biology and medicine. In this study, a microbubble based delivery method was developed. In a high centrifugation field, cells deform and collide with microbubbles to induce intracellular pathways on cell membranes. As a result, biomaterials can then easily enter cells. Experimental results show that this delivery method can achieve high delivery efficiency. Simulation results showed that cells with more deformed structure experienced higher strain on cell membranes than cells with less deformed structure. The models can help explain how centrifugation affects cell membrane permeability. By controlling cell morphology and its mechanical properties, high biomolecule delivery efficiency can be achieved.

  1. Towards in-service acoustic characterization of gaseous micro-bubbles applied to liquid sodium

    Energy Technology Data Exchange (ETDEWEB)

    Baque, F. [CEA Cadarache, DEN/DTN/STPA/LTTS, Bat. 201, 13108 St Paul lez Durance Cedex (France); Cavaro, M. [CEA Cadarache, DEN/DTN/STPA/LIET, Bat. 201, 13108 St Paul lez Durance Cedex (France); Moysan, J.; Corneloup, G. [Laboratoire de Caracterisation Non Destructive (LCND), Universite de la Mediterranee, Aix en Provence, 13625 (France); Sibilo, J. [AREVA-NP, 10 rue Juliette Recamier, 69456 Lyon Cedex 06 (France); Gueudre, C.; Payan, C.; Prele, G.

    2009-07-01

    The characterization of argon micro-bubbles in liquid nitrogen is currently being investigated in connection with the development of Generation IV nuclear reactors. It seems that non-linear acoustic techniques can be used to determine the void fraction (volumetric fraction of free gas) and the histogram of the bubble radii. We discuss the first stage of our work here: the installation of an experimental test bench suitable for generating air micro-bubbles in water and then measuring them optically, before attempting an acoustic characterization. The bubble clouds generated have a radius distribution centred on about 20 microns. (authors)

  2. Coupled-mode induced transparency in aerostatically-tuned microbubble whispering gallery resonators

    CERN Document Server

    Yang, Yong; Ward, Jonathan; Chormaic, Síle Nic

    2015-01-01

    Coupled-mode induced transparency is realized in a single microbubble whispering gallery mode resonator. Using aerostatic tuning, we find that the pressure induced shifting rates are different for different radial order modes. A finite element simulation considering both the strain and stress effects shows a GHz/bar difference and this is confirmed by experiments. A transparency spectrum is obtained when a first order mode shifts across a higher order mode through precise pressure tuning. The resulting lineshapes are fitted with the theory. This work lays a foundation for future applications in microbubble sensing.

  3. Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xi-yuan; LIAO Qing; PU Yi-min; TANG Yong-qiang; GONG Xiao; LI Jia; XU Yan; WANG Zhi-gang

    2009-01-01

    Background Many studies have suggested that the imbalance of angiogenic factor and anti-angiogenic factor expression contributes significantly to the development of choroidal neovascularization (CNV), and ultrasound microbubble combination system can increase the gene transfection efficiency successfully. This study was designed to investigate whether ultrasound-mediated microbubble destruction could effectively deliver therapeutic plasmid into the retina of rat, and whether gene transfer of pigment epithelium-derived factor (PEDF) could inhibit CNV.Methods Human retinal pigment epithelial cells were isolated and treated either with ultrasound or plasmid alone, or with a combination of plasmid, ultrasound and microbubbles to approach feasibility of microbubble-enhanced ultrasound enhance PEDFgene expression; For in vivo animal studies, CNV was induced by argon lasgon laser in rats. These rats were randomly assigned to five groups and were treated by infusing microbubbles attached with the naked plasmid DNA of PEDF into the vitreous of rats followed by immediate ultrasound exposure (intravitreal injection); infusing liposomes with the naked plasmid DNA of PEDF into the vitreous (lipofectamine + PEDF); infusing microbubbles attached with PEDF into the orbit of rats with ultrasound irradiation immediately (retrobular injection); infusing microbubbles attached with PEDF into the femoral vein of rats with exposed to ultrasound immediately (vein injection). The CNV rats without any treatment served as control. Rats were sacrificed and eyes were enucleated at 7, 14, and 28 days after treatment. Gene and protein expression of PEDF was detected by quantitative real-time RT-PCR, Western blotting and immunofluorescence staining, respectively. The effect of PEDF gene transfer on CNV was examined by fluorescein fundus angiography.Results In vitro cell experiments showed that microbubbles with ultrasound irradiation could significantly enhance PEDF delivery as compared with

  4. Detection of acoustic cavitation in the heart with microbubble contrast agents in vivo: a mechanism for ultrasound-induced arrhythmias.

    Science.gov (United States)

    Rota, Claudio; Raeman, Carol H; Child, Sally Z; Dalecki, Diane

    2006-11-01

    Ultrasound fields can produce premature cardiac contractions under appropriate exposure conditions. The pressure threshold for ultrasound-induced premature contractions is significantly lowered when microbubble contrast agents are present in the vasculature. The objective of this study was to measure directly ultrasound-induced cavitation in the murine heart in vivo and correlate the occurrence of cavitation with the production of premature cardiac contractions. A passive cavitation detection technique was used to quantify cavitation activity in the heart. Experiments were performed with anesthetized, adult mice given intravenous injections of either a contrast agent (Optison) or saline. Murine hearts were exposed to ultrasound pulses (200 kHz, 1 ms, 0.1-0.25 MPa). Premature beats were produced in mice injected with Optison and the likelihood of producing a premature beat increased with increasing pressure amplitude. Similarly, cavitation was detected in mice injected with Optison and the amplitude of the passive cavitation detector signal increased with increasing exposure amplitude. Furthermore, there was a direct correlation between the extent of cavitation and the likelihood of ultrasound producing a premature beat. Neither premature beats nor cavitation activity were observed in animals injected with saline and exposed to ultrasound. These results are consistent with acoustic cavitation as a mechanism for this bioeffect.

  5. Quantifiers, Anaphora and Intensionality

    CERN Document Server

    Dalrymple, M; Pereira, F C N; Saraswat, V; Dalrymple, Mary; Lamping, John; Pereira, Fernando; Saraswat, Vijay

    1995-01-01

    The relationship between Lexical-Functional Grammar (LFG) {\\em functional structures} (f-structures) for sentences and their semantic interpretations can be expressed directly in a fragment of linear logic in a way that correctly explains the constrained interactions between quantifier scope ambiguity, bound anaphora and intensionality. This deductive approach to semantic interpretaion obviates the need for additional mechanisms, such as Cooper storage, to represent the possible scopes of a quantified NP, and explains the interactions between quantified NPs, anaphora and intensional verbs such as `seek'. A single specification in linear logic of the argument requirements of intensional verbs is sufficient to derive the correct reading predictions for intensional-verb clauses both with nonquantified and with quantified direct objects. In particular, both de dicto and de re readings are derived for quantified objects. The effects of type-raising or quantifying-in rules in other frameworks here just follow as li...

  6. Plant-mediated CH4 transport and C gas dynamics quantified in-situ in a Phalaris arundinacea-dominant wetland

    DEFF Research Database (Denmark)

    Jensen, Louise Askær; Elberling, Bo; Friborg, Thomas;

    2011-01-01

    Abstract Northern peatland methane (CH4) budgets are important for global CH4 emissions. This study aims to determine the ecosystem CH4 budget and specifically to quantify the importance of Phalaris arundinacea by using different chamber techniques in a temperate wetland. Annually, roughly 70...... passive. Thus, diurnal variations are less important in contrast to wetland vascular plants facilitating convective gas flow. Despite of plant-dominant CH4 transport, net CH4 fluxes were low (–0.005–0.016 µmol m-2 s-1) and annually less than 1% of the annual C-CO2 assimilation. This is considered a result...... of an effective root zone oxygenation resulting in increased CH4 oxidation in the rhizosphere at high water levels. This study shows that although CH4, having a global warming potential 25 times greater than CO2, is emitted from this P. arundinacea wetland, less than 9% of the C sequestered counterbalances the CH...

  7. Actively heated high-resolution fiber-optic-distributed temperature sensing to quantify streambed flow dynamics in zones of strong groundwater upwelling

    Science.gov (United States)

    Briggs, Martin A.; Buckley, Sean F.; Bagtzoglou, Amvrossios C.; Werkema, Dale D.; Lane, John W.

    2016-07-01

    Zones of strong groundwater upwelling to streams enhance thermal stability and moderate thermal extremes, which is particularly important to aquatic ecosystems in a warming climate. Passive thermal tracer methods used to quantify vertical upwelling rates rely on downward conduction of surface temperature signals. However, moderate to high groundwater flux rates (>-1.5 m d-1) restrict downward propagation of diurnal temperature signals, and therefore the applicability of several passive thermal methods. Active streambed heating from within high-resolution fiber-optic temperature sensors (A-HRTS) has the potential to define multidimensional fluid-flux patterns below the extinction depth of surface thermal signals, allowing better quantification and separation of local and regional groundwater discharge. To demonstrate this concept, nine A-HRTS were emplaced vertically into the streambed in a grid with ˜0.40 m lateral spacing at a stream with strong upward vertical flux in Mashpee, Massachusetts, USA. Long-term (8-9 h) heating events were performed to confirm the dominance of vertical flow to the 0.6 m depth, well below the extinction of ambient diurnal signals. To quantify vertical flux, short-term heating events (28 min) were performed at each A-HRTS, and heat-pulse decay over vertical profiles was numerically modeled in radial two dimension (2-D) using SUTRA. Modeled flux values are similar to those obtained with seepage meters, Darcy methods, and analytical modeling of shallow diurnal signals. We also observed repeatable differential heating patterns along the length of vertically oriented sensors that may indicate sediment layering and hyporheic exchange superimposed on regional groundwater discharge.

  8. From Recombination Dynamics to Device Performance: Quantifying the Efficiency of Exciton Dissociation, Charge Separation, and Extraction in Bulk Heterojunction Solar Cells with Fluorine-Substituted Polymer Donors

    KAUST Repository

    Gorenflot, Julien

    2017-09-28

    An original set of experimental and modeling tools is used to quantify the yield of each of the physical processes leading to photocurrent generation in organic bulk heterojunction solar cells, enabling evaluation of materials and processing condition beyond the trivial comparison of device performances. Transient absorption spectroscopy, “the” technique to monitor all intermediate states over the entire relevant timescale, is combined with time-delayed collection field experiments, transfer matrix simulations, spectral deconvolution, and parametrization of the charge carrier recombination by a two-pool model, allowing quantification of densities of excitons and charges and extrapolation of their kinetics to device-relevant conditions. Photon absorption, charge transfer, charge separation, and charge extraction are all quantified for two recently developed wide-bandgap donor polymers: poly(4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b′]dithiophene-3,4-difluorothiophene) (PBDT[2F]T) and its nonfluorinated counterpart poly(4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b′]dithiophene-3,4-thiophene) (PBDT[2H]T) combined with PC71BM in bulk heterojunctions. The product of these yields is shown to agree well with the devices\\' external quantum efficiency. This methodology elucidates in the specific case studied here the origin of improved photocurrents obtained when using PBDT[2F]T instead of PBDT[2H]T as well as upon using solvent additives. Furthermore, a higher charge transfer (CT)-state energy is shown to lead to significantly lower energy losses (resulting in higher VOC) during charge generation compared to P3HT:PCBM.

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

    Directory of Open Access Journals (Sweden)

    Cuiyuan Huang

    2017-07-01

    Full Text Available 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.

  10. New development and application of ultrasound targeted microbubble destruction in gene therapy and drug delivery.

    Science.gov (United States)

    Chen, Zhi-Yi; Yang, Feng; Lin, Yan; Zhang, Jin-Shan; Qiu, Ri-Xiang; Jiang, Lan; Zhou, Xing-Xing; Yu, Jiang-Xiu

    2013-08-01

    Ultrasound is a common used technique for clinical imaging. In recent years, with the advances in preparation technology of microbubbles and the innovations in ultrasound imaging, ultrasound is no longer confined to detection of tissue perfusion, but extends to specific ultrasound molecular imaging and target therapy gradually. With the development of research, ultrasound molecular imaging and target therapy have made great progresses. Targeted microbubbles for molecular imaging are achieved by binding target molecules, specific antibody or ligand to the surface of microbubbles to obtain specific imaging by attaching to target tissues. Meanwhile, it can also achieve targeting gene therapy or drug delivery by ultrasound targeted microbubble destruction (UTMD) mediating genes or drugs to specific target sites. UTMD has a number of advantages, such as target-specific, highly effective, non-invasivity, relatively low-cost and no radiation, and has broad application prospects, which is regarded as one hot spot in medical studies. We reviewed the new development and application of UTMD in gene therapy and drug delivery in this paper. With further development of technology and research, the gene or drug delivery system and related methods will be widely used in application and researches.

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

    Science.gov (United States)

    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).

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

    Science.gov (United States)

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

    2016-07-01

    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.

  13. Nonspherical Shape Oscillations of Coated Microbubbles in Contact With a Wall

    NARCIS (Netherlands)

    Vos, Hendrik J.; Dollet, Benjamin; Versluis, Michel; Jong, de Nico

    2011-01-01

    In this experimental study, the nonspherical and translational behavior of individual coated microbubbles of different sizes, in contact with a 20-μm thickness cellulose wall, are observed and categorized systematically. Images from two orthogonally positioned microscopes are merged and then recorde

  14. Characterizing the Subharmonic Response of Phospholipid-Coated Microbubbles for Carotid Imaging

    NARCIS (Netherlands)

    Faez, Telli; Emmer, Marcia; Docter, Margreet; Sijl, Jeroen; Versluis, Michel; Jong, de Nico

    2011-01-01

    The subharmonic vibration of BR14 (Bracco Research S.A., Geneva, Switzerland) contrast agent microbubbles is investigated within the preferable frequency range for carotid ultrasound imaging (8–12 MHz). The response of the bubbles was recorded optically with an ultra-fast recording camera (Brandaris

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

    Science.gov (United States)

    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.

  16. Enhanced gene expression of systemically administered plasmid DNA inthe liver with therapeutic ultrasound and microbubbles

    NARCIS (Netherlands)

    Raju, B.I.; Leyvi, E.; Seip, R.; Sethuraman, S.; Luo, X.; Bird, A.; Li, S.; Koeberl, D.

    2012-01-01

    Ultrasound mediated delivery (USMD) of novel therapeutic agents in the presence of microbubbles is a potentially safe and effective method for gene therapy offering many desired characteristics such as low toxicity, potential for repeated treatment, and organ specificity.In this study we tested the

  17. Decontamination System Development of Radioative Activated Carbon using Micro-bubbles

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Jong seon; Kim, Wi soo [NESS, Daejeon (Korea, Republic of); Han, Byoung sub. [Enesys Co., Daejeon (Korea, Republic of)

    2016-10-15

    This study was aimed to develop a decontamination system by applying such technical characteristics that minimizes a generation of secondary wastes while decontaminating radiation wastes. The radioactive activated carbon is removed from the end-of-life air cleaning filter in replacement or decommission of nuclear power plant or nuclear facility. By removing radioactive activated carbon, the filter would be classified as a low radioactive contaminant. And thus the amount of radioactive wastes and the treatment cost would be decreased. We are in development of the activated carbon cleaning technique by utilizing micro-bubbles, which improve efficiency and minimize damage of activated carbon. The purpose of using micro-bubbles is to decontamination carbon micropore, which is difficult to access, by principle of cavitation phenomenon generated in collapse of micro-bubbles. In this study, we introduced the micro-bubble decontamination system developed to decontaminate activated carbon. For further researches, we will determine carbon weight change and the decontamination rate under the experimental conditions such as temperature and pH.

  18. Acoustically induced shear stresses in the vicinity of microbubbles in tissue

    DEFF Research Database (Denmark)

    Lewin, Peter A.; Jensen, Leif Bjørnø

    1982-01-01

    The shear stresses in the vicinity of gaseous microbubbles in tissue irradiated by continuous and transient ultrasonic fields typical of those used in diagnostic practice have been calculated from a solution of the equation of motion of the bubble. The assumptions and limitations of the model have...

  19. Microbubble formation and pinch-off scaling exponent in flow-focusing devices

    NARCIS (Netherlands)

    Hoeve, van Wim; Dollet, Benjamin; Versluis, Michel; Lohse, Detlef

    2011-01-01

    We investigate the gas jet breakup and the resulting microbubble formation in a microfluidic flow-focusing device using ultra high-speed imaging at 1 × 106 frames/s. In recent experiments [Dollet et al., Phys. Rev. Lett. 100, 034504 (2008)], it was found that in the final stage of the collapse the r

  20. Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation

    NARCIS (Netherlands)

    Lammers, Twan; Koczera, Patrick; Fokong, Stanley; Gremse, Felix; Ehling, Josef; Vogt, Michael; Pich, Andrij; Storm, Gert; Zandvoort, van Marc; Kiessling, Fabian

    2015-01-01

    Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanop

  1. Theranostic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation

    NARCIS (Netherlands)

    Lammers, Twan; Koczera, Patrick; Fokong, Stanley; Gremse, Felix; Ehling, Josef; Vogt, Michael; Pich, Andrij; Storm, G; Van Zandvoort, Marc; Kiessling, Fabian

    2015-01-01

    Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanop

  2. Sound scattering and localized heat deposition of pulse-driven microbubbles

    NARCIS (Netherlands)

    Hilgenfeldt, Sascha; Lohse, Detlef; Zomack, Michael

    2000-01-01

    The sound scattering of free microbubbles released from strongly driven ultrasound contrast agents with brittle shell (e.g., Sonovist®) is studied numerically. At high peak pressure of the driving pulses, the bubbles respond nonlinearly with cross sections pronouncedly larger than in the linear case

  3. Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces

    NARCIS (Netherlands)

    V. Garbin (Valeria); M. Overvelde (Marlies); B. Dollet (Benjamin); N. de Jong (Nico); D. Lohse (Detlef); M. Versluis (Michel)

    2011-01-01

    textabstractTargeted 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 b

  4. Increase of intracellular cisplatin levels and radiosensitization by ultrasound in combination with microbubbles

    NARCIS (Netherlands)

    Lammertink, Bart H A; Bos, Clemens; van der Wurff-Jacobs, Kim M.; Storm, G; Moonen, Chrit T.; Deckers, Roel

    2016-01-01

    The possibility to enhance drug delivery by using ultrasound in combination with microbubbles (USMB) is extensively studied. So far, these studies have focused on the delivery and efficacy of a single drug, e.g. in chemotherapy. In this study, we investigated the intracellular delivery of cisplatin

  5. The Parametric Images of Microbubbles and Tissue Mimicking Phantoms Based on the Nakagami Parameters Map

    Science.gov (United States)

    Nardjess, Bahbah; Hakim, Djelouah; Bouakaz, A.

    The ultrasonic B-mode imaging is an important clinical tool used to examine internal structures of biological tissue and contrast microbubbles. To overcome the drawbacks of conventional B-scans which cannot fully reflect the nature of the tissue, other imaging methods based on stochastic models are proposed. Among these models, the Nakagami statistical model was chosen, because it is more general and simpler to apply than other statistical models (Rayleigh and K models), to generate parametric images based on the Nakagami parameters. Experiments were performed using a 2.5 MHz linear array connected to an open research platform. A commercially phantom was used to mimic tissue and microbubbles backscatters. For several regions of interest and for different microbubbles dilutions, the RF signals have been generated at 3 and 5 transmit cycles. The Nakagami image can be combined with the use of the B-mode image simultaneously to visualize the tissue and the contrast microbubbles structures for a better medical diagnosis.

  6. Microbubble Beam (MBB), A potential Dispersion Mechanism for Multiphase Gas-Liquid Microreactor Systems

    NARCIS (Netherlands)

    Doku, George N.; Verboom, Willem; Reinhoudt, David N.; Berg, van den Albert

    2003-01-01

    Systems consisting of single and multiple micropipet tips mounted in a channel for the generation of microbubble beams (MBB, as a gas−liquid dispersion mechanism) in moving liquids were constructed in stainless steel housing with Pyrex windows on both sides of the housing for imaging. Pressure head

  7. Robust Whispering-Gallery-Mode Microbubble Lasers from Colloidal Quantum Dots.

    Science.gov (United States)

    Wang, Yue; Ta, Van Duong; Leck, Kheng Swee; Tan, Beng Hau Ian; Wang, Zeng; He, Tingchao; Ohl, Claus-Dieter; Demir, Hilmi Volkan; Sun, Handong

    2017-03-21

    Microlasers hold great promise for the development of photonics and optoelectronics. Among the discovered optical gain materials, colloidal quantum dots (CQDs) have been recognized as the most appealing candidate due to the facile emission tunability and solution processability. However, to date, it is still challenging to develop CQD-based microlasers with low cost yet high performance. Moreover, the poor long-term stability of CQDs remains to be the most critical issue, which may block their laser aspirations. Herein, we developed a unique but generic approach to forming a novel type of a whispering-gallery-mode (WGM) microbubble laser from the hybrid CQD/poly(methyl methacrylate) (PMMA) nanocomposites. The formation mechanism of the microbubbles was unraveled by recording the drying process of the nanocomposite droplets. Interestingly, these microbubbles naturally serve as the high-quality WGM laser resonators. By simply changing the CQDs, the lasing emission can be tuned across the whole visible spectral range. Importantly, these microbubble lasers exhibit unprecedented long-term stability (over one year), sufficient for practical applications. As a proof-of-concept, the potential of water vapor sensing was demonstrated. Our results represent a significant advance in microlasers based on the advantageous CQDs and may offer new possibilities for photonics and optoelectronics.

  8. Application of ultrasound microbubble contrast technology in ophthalmic targeted therapy: literature analysis.

    Science.gov (United States)

    Yuan, Jia-Ying; Zhang, Jian-Hua; Tang, Chong; Zhu, Hong; Xie, Hua; Gao, Shuan-Jie

    2011-01-01

    To analyze the application of microbubble contrast technology in the treatment of ophthalmic diseases, mainly analyzing its advantages and existing problems. A total of 30 representative literatures about the application of ultrasound contrast agent in gene targeted therapy at home and abroad were collected, and focusing on sorting out the literature reporting the treatment of ophthalmic diseases with microbubble contrast technology in recent years, then recalling its advantages and problems, finally making reasonable assessment on existing problems and proposing possible solutions to the problems. DUE TO ITS UNIQUE SAFETY AND EFFICACY, THE TREATMENT OF OPHTHALMIC DISEASES WITH MICROBUBBLE CONTRAST TECHNOLOGY HAS INCREASINGLY DRAWN THE ATTENTION OF CLINICIANS, BUT TWO RELEVANT ISSUES SHOULD BE CONSIDERED: first, the nature of contrast agent and the choice of corresponding ultrasound parameters; second, relative incidence of tissue bleeding, intravascular hemolysis, moderate or severe allergy as well as other side effects. Microbubble may become the carrier of targeted therapy, and as a kind of new non-invasive delivery system, the ultrasound contrast agent has broad application prospects, but its application in ophthalmic research is still in its initial stage and the safety of contrast-enhanced ultrasound still needs further study.

  9. The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid-shelled microbubble contrast agent.

    Science.gov (United States)

    Shekhar, Himanshu; Awuor, Ivy; Thomas, Keri; Rychak, Joshua J; Doyley, Marvin M

    2014-04-01

    Characterizing the non-linear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this article, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized non-linear emissions from Targestar-p microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 min, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12-15 and 5-8 dB) after 5-10 min of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2-5 dB. The temporal changes in the non-linear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, non-linear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving non-linear imaging by careful design of ultrasound contrast agents.

  10. Drug-Loaded Nano/Microbubbles for Combining Ultrasonography and Targeted Chemotherapy

    Science.gov (United States)

    Gao, Zhonggao; Kennedy, Anne M.; Christensen, Douglas A.; Rapoport, Natalya Y.

    2008-01-01

    A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique. PMID:18096196

  11. Effect of cavity pressure on the performance of the explosive micro-bubble actuator

    NARCIS (Netherlands)

    van den Broek, D.M.; Elwenspoek, Michael Curt

    The explosive micro-bubble actuator is a new type of actuator based on bubble generation by explosive evaporation. It can operate at frequencies up to 5 kHz which is extremely high for a thermo-pneumatic actuator. At these frequencies, the device can still produce a pressure of several bars

  12. ULTRASOUND AND MICROBUBBLE-INDUCED LOCAL DELIVERY OF MICRORNA-BASED THERAPEUTICS

    NARCIS (Netherlands)

    Kwekkeboom, Rick F. J.; Lei, Zhiyong; Bogaards, Sylvia J. P.; Aiazian, Eric; Kamp, Otto; Paulus, Walter J.; Sluijter, Joost P. G.; Musters, Rene J. P.

    2015-01-01

    MicroRNAs are involved in many pathologic processes and are a promising target for therapeutic intervention. However, successful, localized delivery of microRNA-based therapeutics is lacking. In this study, cationic ultrasound-responsive microbubbles (MBs) were used to deliver microRNA blockers and

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  15. Effects of Purge-Flow Rate on Microbubble Capture in Radial Arterial-Line Filters.

    Science.gov (United States)

    Herbst, Daniel P

    2016-09-01

    The process of microbubble filtration from blood is complex and highly dependent on the forces of flow and buoyancy. To protect the patient from air emboli, arterial-line filters commonly use a micropore screen, a large volume housing with purpose-built shape, and a purge port to trap, separate, and remove circulating microbubbles. Although it has been proposed that an insufficient buoyancy force renders the purge port ineffective at removing microbubbles smaller than 500 μm, this research attempts to investigate the purge flow of an arterial-line filter to better understand the microbubble removal function in a typical radial filter design. As its primary objective, the study aims to determine the effect of purge-flow rate on bubble capture using air bolus injections from a syringe pump with 22-gauge needle and Doppler ultrasound bubble detection. The measureable bubble size generated in the test circuit ranged between 30 and 500 μm, while purge flow was varied between .1 and .5 L/min for testing. Statistical analysis of the test data was handled using a repeated measures design with significance set at p purge flows yielded higher bubble counts, but the effect of purge-flow rate on bubble capture decreased as bubble size increased. Results also showed that purge flow from the test filter was capable of capturing all bubble sizes being generated over the entire flow range tested, and confirms utility of the purge port in removing microbubbles smaller than 500 μm. By analyzing bubble counts in the purge flow of a typical radial-filter design, this study demonstrates that currently available micropore filter technology is capable of removing the size range of bubbles that commonly pass through modern pump-oxygenator systems and should continue to be considered during extracorporeal circulation as a measure to improve patient safety.

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

    Science.gov (United States)

    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

  17. Decomposing generalized quantifiers

    NARCIS (Netherlands)

    Westerståhl, D.

    2008-01-01

    This note explains the circumstances under which a type <1> quantifier can be decomposed into a type <1, 1> quantifier and a set, by fixing the first argument of the former to the latter. The motivation comes from the semantics of Noun Phrases (also called Determiner Phrases) in natural languages, b

  18. Decomposing generalized quantifiers

    NARCIS (Netherlands)

    Westerståhl, D.

    2008-01-01

    This note explains the circumstances under which a type <1> quantifier can be decomposed into a type <1, 1> quantifier and a set, by fixing the first argument of the former to the latter. The motivation comes from the semantics of Noun Phrases (also called Determiner Phrases) in natural languages,

  19. Understanding quantifiers in language

    NARCIS (Netherlands)

    Szymanik, J.; Zajenkowski, M.; Taatgen, N.; van Rijn, H.

    2009-01-01

    We compare time needed for understanding different types of quantifiers. We show that the computational distinction between quantifiers recognized by finite-automata and push-down automata is psychologically relevant. Our research improves upon hypothesis and explanatory power of recent neuroimaging

  20. Experimental research on wild-type p53 plasmid transfected into retinoblastoma cells and tissues using an ultrasound microbubble intensifier.

    Science.gov (United States)

    Luo, J; Zhou, X; Diao, L; Wang, Z

    2010-01-01

    The transfection efficiency of wild-type p53 (wtp53) was investigated in retinoblastoma (RB) Y79 cells using an ultrasound microbubble technique. A human RB nude mouse xenograft tumour model was also used to investigate whether this technique could deliver wtp53 into solid tumours. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that wtp53 was successfully transfected into Y79 cells in the plasmid with microbubbles and ultrasound group and in the plasmid with liposomes group, but not in the plasmid with ultrasound group or in the untreated control group. Flow cytometry showed that apoptosis was highest in the microbubbles and ultrasound group (25.58%) compared with the plasmid with liposomes group (19.50%), and the other two groups (microbubbles and ultrasound group. This study provides preliminary evidence in support of a potential new approach to RB gene therapy.

  1. Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles.

    Science.gov (United States)

    Yang, D; Gao, Y-H; Tan, K-B; Zuo, Z-X; Yang, W-X; Hua, X; Li, P-J; Zhang, Y; Wang, G

    2013-12-01

    We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (Pliposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

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

    Science.gov (United States)

    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.

  3. An automated sleep-state classification algorithm for quantifying sleep timing and sleep-dependent dynamics of electroencephalographic and cerebral metabolic parameters

    Directory of Open Access Journals (Sweden)

    Rempe MJ

    2015-09-01

    Full Text Available Michael J Rempe,1,2 William C Clegern,2 Jonathan P Wisor2 1Mathematics and Computer Science, Whitworth University, Spokane, WA, USA; 2College of Medical Sciences and Sleep and Performance Research Center, Washington State University, Spokane, WA, USAIntroduction: Rodent sleep research uses electroencephalography (EEG and electromyography (EMG to determine the sleep state of an animal at any given time. EEG and EMG signals, typically sampled at >100 Hz, are segmented arbitrarily into epochs of equal duration (usually 2–10 seconds, and each epoch is scored as wake, slow-wave sleep (SWS, or rapid-eye-movement sleep (REMS, on the basis of visual inspection. Automated state scoring can minimize the burden associated with state and thereby facilitate the use of shorter epoch durations.Methods: We developed a semiautomated state-scoring procedure that uses a combination of principal component analysis and naïve Bayes classification, with the EEG and EMG as inputs. We validated this algorithm against human-scored sleep-state scoring of data from C57BL/6J and BALB/CJ mice. We then applied a general homeostatic model to characterize the state-dependent dynamics of sleep slow-wave activity and cerebral glycolytic flux, measured as lactate concentration.Results: More than 89% of epochs scored as wake or SWS by the human were scored as the same state by the machine, whether scoring in 2-second or 10-second epochs. The majority of epochs scored as REMS by the human were also scored as REMS by the machine. However, of epochs scored as REMS by the human, more than 10% were scored as SWS by the machine and 18 (10-second epochs to 28% (2-second epochs were scored as wake. These biases were not strain-specific, as strain differences in sleep-state timing relative to the light/dark cycle, EEG power spectral profiles, and the homeostatic dynamics of both slow waves and lactate were detected equally effectively with the automated method or the manual scoring

  4. Low Intensity Ultrasound Mediated Liposomal Doxorubicin Delivery Using Polymer Microbubbles.

    Science.gov (United States)

    Yu, Francois T H; Chen, Xucai; Wang, Jianjun; Qin, Bin; Villanueva, Flordeliza S

    2016-01-01

    Cardiotoxicity is the major dose-limiting factor in the chemotherapeutic use of doxorubicin (Dox). A delivery vehicle that can be triggered to release its payload in the tumoral microvasculature but not in healthy tissue would help improve the therapeutic window of the drug. Delivery strategies combining liposomal encapsulated Dox (LDox), microbubbles (MBs), and ultrasound (US) have been shown to improve therapeutic efficacy of LDox, but much remains to be known about the mechanisms and the US conditions that maximize cytotoxicity using this approach. In this study, we compared different US pulses in terms of drug release and acute toxicity. Drug uptake and proliferation rates using low-intensity US were measured in squamous cell carcinoma cells exposed to LDox conjugated to or coinjected with polymer MBs. The aims of this study were: (1) to compare the effects of low- and high-pressure US on Dox release kinetics; (2) to evaluate whether conjugating the liposome to the MB surface (DoxLPX) is an important factor for drug release and cytotoxicity; and (3) to determine which US parameters most inhibit cell proliferation and whether this inhibition is mediated by drug release or the MB/US interaction with cells. Low-pressure US (170 kPa) at high duty cycle (stable cavitation) released up to ∼ 70% of the encapsulated Dox from the DoxLPX, thus improving Dox bioavailability and cellular uptake and leading to a significant reduction in cell proliferation at 48 h. Flow cytometry showed that US generating stable oscillations of DoxLPX significantly increased cellular Dox uptake at 4 h after US exposure compared to LDox. Drug uptake was correlated with cytotoxicity at 48 h. Our results demonstrate that Dox-containing liposomes conjugated to polymer MBs can be triggered to release ∼ 70% of their payload using noninertial US. Following release, Dox became bioavailable to the cells and induced significantly higher cytotoxicity compared to nonreleased encapsulated drug. Our

  5. Whole-atmosphere aerosol microphysics simulations of the Mt Pinatubo eruption: Part 2: Quantifying the direct and indirect (dynamical) radiative forcings

    Science.gov (United States)

    Mann, Graham; Dhomse, Sandip; Carslaw, Ken; Chipperfield, Martyn; Lee, Lindsay; Emmerson, Kathryn; Abraham, Luke; Telford, Paul; Pyle, John; Braesicke, Peter; Bellouin, Nicolas; Dalvi, Mohit; Johnson, Colin

    2016-04-01

    The Mt Pinatubo volcanic eruption in June 1991 injected between 10 and 20 Tg of sulphur dioxide into the tropical lower stratosphere. Following chemical conversion to sulphuric acid, the stratospheric aerosol layer thickened substantially causing a strong radiative, dynamical and chemical perturbation to the Earth's atmosphere with effects lasting several years. In this presentation we show results from model experiments to isolate the different ways the enhanced stratospheric aerosol from Pinatubo influenced the Earth's climate. The simulations are carried out in the UK Chemistry and Aerosol composition-climate model (UKCA) which extends the high-top (to 80km) version of the UK Met Office Unified Model (UM). The UM-UKCA model uses the GLOMAP-mode aerosol microphysics module coupled with a stratosphere-troposphere chemistry scheme including sulphur chemistry. By running no-feedback and standard integrations, we separate the main radiative forcings due to aerosol-radiation interactions (i.e. the direct forcings) from those induced by dynamical changes which alter meridional heat transport and distributions of aerosol, ozone and water vapour.

  6. Connected Car: Quantified Self becomes Quantified Car

    Directory of Open Access Journals (Sweden)

    Melanie Swan

    2015-02-01

    Full Text Available The automotive industry could be facing a situation of profound change and opportunity in the coming decades. There are a number of influencing factors such as increasing urban and aging populations, self-driving cars, 3D parts printing, energy innovation, and new models of transportation service delivery (Zipcar, Uber. The connected car means that vehicles are now part of the connected world, continuously Internet-connected, generating and transmitting data, which on the one hand can be helpfully integrated into applications, like real-time traffic alerts broadcast to smartwatches, but also raises security and privacy concerns. This paper explores the automotive connected world, and describes five killer QS (Quantified Self-auto sensor applications that link quantified-self sensors (sensors that measure the personal biometrics of individuals like heart rate and automotive sensors (sensors that measure driver and passenger biometrics or quantitative automotive performance metrics like speed and braking activity. The applications are fatigue detection, real-time assistance for parking and accidents, anger management and stress reduction, keyless authentication and digital identity verification, and DIY diagnostics. These kinds of applications help to demonstrate the benefit of connected world data streams in the automotive industry and beyond where, more fundamentally for human progress, the automation of both physical and now cognitive tasks is underway.

  7. A Probabilistic Analysis to Quantify the Effect of March 11, 2004, Attacks in Madrid on the March 14 Elections in Spain: A Dynamic Modelling Approach

    Directory of Open Access Journals (Sweden)

    Juan-Carlos Cortés

    2015-01-01

    Full Text Available The bomb attacks in Madrid three days before the general elections of March 14, 2004, and their possible influence on the victory of PSOE (Spanish Workers Socialist Party, defeating PP (Popular Party, have been a matter of study from several points of view (i.e., sociological, political, or statistical. In this paper, we present a dynamic model based on a system of differential equations such that it, using data from Spanish CIS (National Center of Sociological Research, describes the evolution of voting intention of the Spanish people over time. Using this model, we conclude that the probability is very low that the PSOE would have won had the attack not happened. Moreover, after the attack, the PSOE increased an average of 5.6% in voting on March 14 and an average of 11.2% of the Spanish people changed their vote between March 11 and March 14. These figures are in accordance with other studies.

  8. Ultrasound-triggered release of materials entrapped in microbubble-liposome constructs: a tool for targeted drug delivery.

    Science.gov (United States)

    Klibanov, Alexander L; Shevchenko, Talent I; Raju, Balasundar I; Seip, Ralf; Chin, Chien T

    2010-11-20

    We investigated the preparation of ultrasound-triggered drug delivery system, based on a pendant complex of microbubble coated with liposomes. Biotinylated decafluorobutane microbubbles were coated with biotinylated liposomes via a streptavidin linker. Liposomes were prepared incorporating calcein and thrombin. Based on initial concentration of calcein, over 1 um(3) payload volume per each microbubble-liposome particle was achieved, when 100 nm liposomes were used. Insonation of microbubble-liposome pendants in vitro resulted in the complete destruction of microbubbles and triggered release of a significant fraction of the entrapped material. Treatment with 1MHz ultrasound (5 pulses, 100 ms, 7 MPa peak negative acoustic pressure) resulted in the release of ~30% of entrapped calcein, as estimated by the fluorescence quenching assay. Thrombin release from liposomes complexed with microbubbles (11% of entrapped material) due to ultrasound treatment was estimated by a chromogenic substrate study. Prior to insonation, substrate hydrolysis was at background level. Ultrasound-triggered release of thrombin from the pendant complexes caused an acceleration of blood clotting.

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

    Science.gov (United States)

    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.

  10. Influencing factors on microbubble ozonation treatment of acid red 3R wastewater

    Directory of Open Access Journals (Sweden)

    Yurong YA

    2017-08-01

    Full Text Available The microbubble ozonation was used to treat acid red 3R wastewater in order to investigate the influencing factors on its performance. The effects of ozone dose, initial acid red 3R concentration and activated carbon on the performance of microbubble ozonation treatment of acid red 3R wastewater are investigated. The decolorization rate, TOC removal rate, pH variation and ozone utilization efficiency in the microbubble ozonation treatment are compared under different treatment conditions. The results indicate that when increasing ozone dose or decreasing initial acid red 3R concentration, both decolorization rate and TOC removal rate of acid red 3R wastewater increase, but ozone utilization efficiency decreases. The coal-based activated carbon shows strong catalytic activity for microbubble ozonation, which could enhance the decolorization rate and TOC removal rate of acid red 3R wastewater. The better performance of microbubble ozonation treatment is achieved when the ozone dose is 48.3 mg/min and the initial acid red 3R mass concentration is 100 mg/L. Under these conditions, the decolorization efficiency reaches to 100% after treatment for 30 min, the TOC removal efficiency reaches to 78.0% after treatment for 120 min, the reaction rate constant of TOC removal is 0.015 min-1 and the ozone utilization efficiency is higher than 99%. With addition of the coal-based activated carbon of 5 g/L, the decolorization efficiency reaches to 100% after treatment for 15 min, the TOC removal efficiency reaches to 91.2% after treatment for 120 min and the reaction rate constant of TOC removal increases to 0037 min-1.The accumulation and following degradation of intermediate products of small molecule organic acid happens during treatment process, and as a result, the solution pH decreases initially and then increases. Therefore, the optimization of influencing factors for microbubble ozonation could increase both contaminant removal

  11. The diagnostic value of small bowel wall vascularity after sulfur hexafluoride-filled microbubble injection in patients with Crohn's disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment

    Energy Technology Data Exchange (ETDEWEB)

    Quaia, Emilio [Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste (Italy)], E-mail: quaia@units.it; Migaleddu, Vincenzo [Sardinian Mediterranean Imaging Research Group - SMIRG no profit foundation, Via Gorizia no 11 07100 Sassari (Italy); Baratella, Elisa; Pizzolato, Riccardo; Rossi, Alexia; Grotto, Maurizio; Cova, Maria Assunta [Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste (Italy)

    2009-03-15

    Purpose: To assess the value of small bowel wall vascularity after microbubble contrast agent injection in evaluating the therapeutic effectiveness of specific anti-inflammatory treatment in patients with Crohn's disease. Materials and methods: Fifteen patients (7 male and 8 female; mean age {+-} SD, 40 years {+-} 6) with a biopsy-proven diagnosis of Crohn's disease - Crohn's disease activity index (CDAI) > 150 (n = 12 patients) or <150 (n = 3) - involving the terminal loop of the small bowel (wall thickness >5 mm) were included. In each patient the terminal loop was scanned by contrast-enhanced ultrasound (CEUS) after sulfur hexafluoride-filled microbubble injection before and after 6-month anti-inflammatory treatment. The vascularity of the terminal loop was quantified in gray-scale levels (0-255) by a manually drawn ROI encompassing the thickened bowel wall and it was correlated with CDAI. Result: Before the beginning of the specific treatment all patients revealed diffuse transparietal contrast enhancement after microbubble injection, except for 3 patients who revealed contrast enhancement limited to the submucosa. In 13 patients the slope of the first ascending tract and the area under the enhancement curve were significantly lower after anti-inflammatory treatment (P < 0.05; Wilcoxon test) with a significant correlation with the CDAI score ({rho} = 0.85, P < 0.05). In 2 patients no significant vascularity changes were found even though a mild reduction of CDAI score was identified (from 200 to 150 gray-scale levels). Conclusion: CEUS is a useful method to assess the therapeutic effectiveness of specific medical anti-inflammatory treatment in patients with Crohn's disease.

  12. Submersible UV-Vis spectroscopy for quantifying streamwater organic carbon dynamics: implementation and challenges before and after forest harvest in a headwater stream.

    Science.gov (United States)

    Jollymore, Ashlee; Johnson, Mark S; Hawthorne, Iain

    2012-01-01

    Organic material, including total and dissolved organic carbon (DOC), is ubiquitous within aquatic ecosystems, playing a variety of important and diverse biogeochemical and ecological roles. Determining how land-use changes affect DOC concentrations and bioavailability within aquatic ecosystems is an important means of evaluating the effects on ecological productivity and biogeochemical cycling. This paper presents a methodology case study looking at the deployment of a submersible UV-Vis absorbance spectrophotometer (UV-Vis spectro::lyzer model, s::can, Vienna, Austria) to determine stream organic carbon dynamics within a headwater catchment located near Campbell River (British Columbia, Canada). Field-based absorbance measurements of DOC were made before and after forest harvest, highlighting the advantages of high temporal resolution compared to traditional grab sampling and laboratory measurements. Details of remote deployment are described. High-frequency DOC data is explored by resampling the 30 min time series with a range of resampling time intervals (from daily to weekly time steps). DOC export was calculated for three months from the post-harvest data and resampled time series, showing that sampling frequency has a profound effect on total DOC export. DOC exports derived from weekly measurements were found to underestimate export by as much as 30% compared to DOC export calculated from high-frequency data. Additionally, the importance of the ability to remotely monitor the system through a recently deployed wireless connection is emphasized by examining causes of prior data losses, and how such losses may be prevented through the ability to react when environmental or power disturbances cause system interruption and data loss.

  13. Submersible UV-Vis Spectroscopy for Quantifying Streamwater Organic Carbon Dynamics: Implementation and Challenges before and after Forest Harvest in a Headwater Stream

    Directory of Open Access Journals (Sweden)

    Iain Hawthorne

    2012-03-01

    Full Text Available Organic material, including total and dissolved organic carbon (DOC, is ubiquitous within aquatic ecosystems, playing a variety of important and diverse biogeochemical and ecological roles. Determining how land-use changes affect DOC concentrations and bioavailability within aquatic ecosystems is an important means of evaluating the effects on ecological productivity and biogeochemical cycling. This paper presents a methodology case study looking at the deployment of a submersible UV-Vis absorbance spectrophotometer (UV-Vis spectro::lyzer model, s::can, Vienna, Austria to determine stream organic carbon dynamics within a headwater catchment located near Campbell River (British Columbia, Canada. Field-based absorbance measurements of DOC were made before and after forest harvest, highlighting the advantages of high temporal resolution compared to traditional grab sampling and laboratory measurements. Details of remote deployment are described. High-frequency DOC data is explored by resampling the 30 min time series with a range of resampling time intervals (from daily to weekly time steps. DOC export was calculated for three months from the post-harvest data and resampled time series, showing that sampling frequency has a profound effect on total DOC export. DOC exports derived from weekly measurements were found to underestimate export by as much as 30% compared to DOC export calculated from high-frequency data. Additionally, the importance of the ability to remotely monitor the system through a recently deployed wireless connection is emphasized by examining causes of prior data losses, and how such losses may be prevented through the ability to react when environmental or power disturbances cause system interruption and data loss.

  14. Material characterization of the encapsulation of an ultrasound contrast microbubble and its subharmonic response: strain-softening interfacial elasticity model.

    Science.gov (United States)

    Paul, Shirshendu; Katiyar, Amit; Sarkar, Kausik; Chatterjee, Dhiman; Shi, William T; Forsberg, Flemming

    2010-06-01

    Two nonlinear interfacial elasticity models--interfacial elasticity decreasing linearly and exponentially with area fraction--are developed for the encapsulation of contrast microbubbles. The strain softening (decreasing elasticity) results from the decreasing association between the constitutive molecules of the encapsulation. The models are used to find the characteristic properties (surface tension, interfacial elasticity, interfacial viscosity and nonlinear elasticity parameters) for a commercial contrast agent. Properties are found using the ultrasound attenuation measured through a suspension of contrast agent. Dynamics of the resulting models are simulated, compared with other existing models and discussed. Imposing non-negativity on the effective surface tension (the encapsulation experiences no net compressive stress) shows "compression-only" behavior. The exponential and the quadratic (linearly varying elasticity) models result in similar behaviors. The validity of the models is investigated by comparing their predictions of the scattered nonlinear response for the contrast agent at higher excitations against experimental measurement. All models predict well the scattered fundamental response. The nonlinear strain softening included in the proposed elastic models of the encapsulation improves their ability to predict subharmonic response. They predict the threshold excitation for the initiation of subharmonic response and its subsequent saturation.

  15. Quantifying the spatio-temporal pattern of the ground impact of space weather events using dynamical networks formed from the SuperMAG database of ground based magnetometer stations.

    Science.gov (United States)

    Dods, Joe; Chapman, Sandra; Gjerloev, Jesper

    2016-04-01

    Quantitative understanding of the full spatial-temporal pattern of space weather is important in order to estimate the ground impact. Geomagnetic indices such as AE track the peak of a geomagnetic storm or substorm, but cannot capture the full spatial-temporal pattern. Observations by the ~100 ground based magnetometers in the northern hemisphere have the potential to capture the detailed evolution of a given space weather event. We present the first analysis of the full available set of ground based magnetometer observations of substorms using dynamical networks. SuperMAG offers a database containing ground station magnetometer data at a cadence of 1min from 100s stations situated across the globe. We use this data to form dynamic networks which capture spatial dynamics on timescales from the fast reconfiguration seen in the aurora, to that of the substorm cycle. Windowed linear cross-correlation between pairs of magnetometer time series along with a threshold is used to determine which stations are correlated and hence connected in the network. Variations in ground conductivity and differences in the response functions of magnetometers at individual stations are overcome by normalizing to long term averages of the cross-correlation. These results are tested against surrogate data in which phases have been randomised. The network is then a collection of connected points (ground stations); the structure of the network and its variation as a function of time quantify the detailed dynamical processes of the substorm. The network properties can be captured quantitatively in time dependent dimensionless network parameters and we will discuss their behaviour for examples of 'typical' substorms and storms. The network parameters provide a detailed benchmark to compare data with models of substorm dynamics, and can provide new insights on the similarities and differences between substorms and how they correlate with external driving and the internal state of the

  16. Transfection effect of microbubbles on cells in superposed ultrasound waves and behavior of cavitation bubble.

    Science.gov (United States)

    Kodama, Tetsuya; Tomita, Yukio; Koshiyama, Ken-Ichiro; Blomley, Martin J K

    2006-06-01

    The combination of ultrasound and ultrasound contrast agents (UCAs) is able to induce transient membrane permeability leading to direct delivery of exogenous molecules into cells. Cavitation bubbles are believed to be involved in the membrane permeability; however, the detailed mechanism is still unknown. In the present study, the effects of ultrasound and the UCAs, Optison on transfection in vitro for different medium heights and the related dynamic behaviors of cavitation bubbles were investigated. Cultured CHO-E cells mixed with reporter genes (luciferase or beta-gal plasmid DNA) and UCAs were exposed to 1 MHz ultrasound in 24-well plates. Ultrasound was applied from the bottom of the well and reflected at the free surface of the medium, resulting in the superposition of ultrasound waves within the well. Cells cultured on the bottom of 24-well plates were located near the first node (displacement node) of the incident ultrasound downstream. Transfection activity was a function determined with the height of the medium (wave traveling distance), as well as the concentration of UCAs and the exposure time was also determined with the concentration of UCAs and the exposure duration. Survival fraction was determined by MTT assay, also changes with these values in the reverse pattern compared with luciferase activity. With shallow medium height, high transfection efficacy and high survival fraction were obtained at a low concentration of UCAs. In addition, capillary waves and subsequent atomized particles became significant as the medium height decreased. These phenomena suggested cavitation bubbles were being generated in the medium. To determine the effect of UCAs on bubble generation, we repeated the experiments using crushed heat-treated Optison solution instead of the standard microbubble preparation. The transfection ratio and survival fraction showed no additional benefit when ultrasound was used. These results suggested that cavitation bubbles created by the

  17. Measurement of real pulsatile blood flow using X-ray PIV technique with CO2 microbubbles.

    Science.gov (United States)

    Park, Hanwook; Yeom, Eunseop; Seo, Seung-Jun; Lim, Jae-Hong; Lee, Sang-Joon

    2015-03-06

    Synchrotron X-ray imaging technique has been used to investigate biofluid flows in a non-destructive manner. This study aims to investigate the feasibility of the X-ray PIV technique with CO2 microbubbles as flow tracer for measurement of pulsatile blood flows under in vivo conditions. The traceability of CO2 microbubbles in a pulsatile flow was demonstrated through in vitro experiment. A rat extracorporeal bypass loop was used by connecting a tube between the abdominal aorta and jugular vein of a rat to obtain hemodynamic information of actual pulsatile blood flows without changing the hemorheological properties. The decrease in image contrast of the surrounding tissue was also investigated for in vivo applications of the proposed technique. This technique could be used to accurately measure whole velocity field information of real pulsatile blood flows and has strong potential for hemodynamic diagnosis of cardiovascular diseases.

  18. Ultrasound imaging of oxidative stress in vivo with chemically-generated gas microbubbles.

    Science.gov (United States)

    Perng, John Kangchun; Lee, Seungjun; Kundu, Kousik; Caskey, Charles F; Knight, Sarah F; Satir, Sarp; Ferrara, Katherine W; Taylor, W Robert; Degertekin, F Levent; Sorescu, Daniel; Murthy, Niren

    2012-09-01

    Ultrasound contrast agents (UCAs) have tremendous potential for in vivo molecular imaging because of their high sensitivity. However, the diagnostic potential of UCAs has been difficult to exploit because current UCAs are based on pre-formed microbubbles, which can only detect cell surface receptors. Here, we demonstrate that chemical reactions that generate gas forming molecules can be used to perform molecular imaging by ultrasound in vivo. This new approach was demonstrated by imaging reactive oxygen species in vivo with allylhydrazine, a liquid compound that is converted into nitrogen and propylene gas after reacting with radical oxidants. We demonstrate that allylhydrazine encapsulated within liposomes can detect a 10 micromolar concentration of radical oxidants by ultrasound, and can image oxidative stress in mice, induced by lipopolysaccharide, using a clinical ultrasound system. We anticipate numerous applications of chemically-generated microbubbles for molecular imaging by ultrasound, given ultrasound's ability to detect small increments above the gas saturation limit, its spatial resolution and widespread clinical use.

  19. Targeted Delivery of Nanoparticles Bearing Fibroblast Growth Factor-2 by Ultrasonic Microbubble Destruction for Therapeutic Arteriogenesis

    Science.gov (United States)

    Chappell, John C.; Song, Ji; Burke, Caitlin W.

    2009-01-01

    Therapeutic strategies in which recombinant growth factors are injected to stimulate arteriogenesis in patients suffering from occlusive vascular disease stand to benefit from improved targeting, less invasiveness, better growth-factor stability, and more sustained growth-factor release. A microbubble contrast-agent-based system facilitates nanoparticle deposition in tissues that are targeted by 1-MHz ultrasound. This system can then be used to deliver poly(d,l-lactic-co-glycolic acid) nanoparticles containing fibroblast growth factor-2 to mouse adductor muscles in a model of hind-limb arterial insufficiency. Two weeks after treatment, significant increases in both the caliber and total number of collateral arterioles are observed, indicating that the delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction may represent an effective and minimally invasive strategy for the targeted stimulation of therapeutic arteriogenesis. PMID:18720443

  20. Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded (TRUME) light

    CERN Document Server

    Ruan, Haowen; Yang, Changhuei

    2015-01-01

    Focusing light inside scattering media in a freely addressable fashion is challenging, as the wavefront of the scattered light is highly disordered. Recently developed ultrasound-guided wavefront shaping methods are addressing this challenge, albeit with relatively low modulation efficiency and resolution limitations. In this paper, we present a new technique, time-reversed ultrasound microbubble encoded (TRUME) optical focusing, which is able to focus light with improved efficiency and sub-ultrasound wavelength resolution. This method ultrasonically destructs microbubbles, and measures the wavefront change to compute and render a suitable time-reversed wavefront solution for focusing. We demonstrate that the TRUME technique can create an optical focus at the site of bubble destruction with a size of ~2 microns. Due to the nonlinear pressure-to-destruction response, the TRUME technique can break the addressable focus resolution barrier imposed by the ultrasound focus. We experimentally demonstrate a 2-fold ad...

  1. A misinterpreted case of aorta prosthesis endocarditis: remember the phenomenon of microbubbles.

    Science.gov (United States)

    Lerche, Christian Johann; Haugan, Ketil Jørgen; Reimers, Jesper Irving; Ihlemann, Nikolaj

    2013-08-01

    A 17-year-old male with a history of newly implanted mechanical valve at the aortic position, presented with fever, rigors, and painful cutaneous abscesses on his lower extremities and was suspected for infective endocarditis. Transthoracic echocardiography (TTE) showed a vegetation-like structure following the movement of the mechanical heart valve (MHV), which eventually proved to be a product of degassing microbubbles (MB).

  2. Characterisation of contrast agent microbubbles for ultrasound imaging and therapy research

    OpenAIRE

    2016-01-01

    The high efficiency with which gas microbubbles can scatter ultrasound compared to 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...

  3. Subharmonic scattering of phospholipid-shell microbubbles at low acoustic pressure amplitudes.

    Science.gov (United States)

    Frinking, Peter J A; Brochot, Jean; Arditi, Marcel

    2010-08-01

    Subharmonic scattering of phospholipid-shell microbubbles excited at relatively low acoustic pressure amplitudes (<30 kPa) has been associated with echo responses from compression-only bubbles having initial surface tension values close to zero. In this work, the relation between sbharmonics and compression-only behavior of phospholipid-shell microbubbles was investigated, experimentally and by simulation, as a function of the initial surface tension by applying ambient overpressures of 0 and 180 mmHg. The microbubbles were excited using a 64-cycle transmit burst with a center frequency of 4 MHz and peak-negative pressure amplitudes ranging from 20 of 150 kPa. In these conditions, an increase in subharmonic response of 28.9 dB (P < 0.05) was measured at 50 kPa after applying an overpressure of 180 mmHg. Simulations using the Marmottant model, taking into account the effect of ambient overpressure on bubble size and initial surface tension, confirmed the relation between subharmonics observed in the pressure-time curves and compression-only behavior observed in the radius-time curves. The trend of an increase in subharmonic response as a function of ambient overpressure, i.e., as a function of the initial surface tension, was predicted by the model. Subharmonics present in the echo responses of phospholipid-shell microbubbles excited at low acoustic pressure amplitudes are indeed related to the echo responses from compression-only bubbles. The increase in subharmonics as a function of ambient overpressure may be exploited for improving methods for noninvasive pressure measurement in heart cavities or big vessels in the human body.

  4. [Influencing factors for operational performance of a biofilm reactor with microbubble aeration using SPG membrane].

    Science.gov (United States)

    Zhang, Lei; Zhang, Ming; Liu, Chun; Zhang, Jing; Liu, Jun-Liang

    2014-08-01

    The microbubble-aerated biofilm reactor provides a feasibility to apply microbubble aeration in aerobic wastewater treatment processes. In this study, Shirasu porous glass (SPG) membranes were used for microbubble aeration in a fixed bed biofilm reactor treating synthetic municipal wastewater. The influencing factors for operational performance of the bioreactor were investigated, including operating parameters, SPG membrane fouling and its structural changes. The results indicated that there was no significant influences of air flux, organic loading rate and packed bed on COD removal and an average COD removal efficiency of 80% -90% could be achieved under different operating conditions. On the other hand, the dissolved oxygen (DO) concentrations decreased significantly along with reducing air flux or increasing organic loading rate. As a result, the ammonia removal deteriorated gradually and the average ammonia removal efficiency decreased from 80% -90% to 20% -30% At the same time, the total nitrogen (TN) removal achieved in the simultaneous nitrification and denitrification process was also reduced from 30% -40% to about 20% , due to nitrification inhibition. Higher available porosity could be obtained when ring packing was used in the fixed bed, resulting in improvement of contaminant removal performance. An oxygen utilization efficiency of close to 100% could be achieved at low air fluxes or high organic loading rates during microbubble aeration. Both biofilm growth and organic foulant accumulation on SPC, membrane surface contributed to membrane fouling after long-term operation. The average pore size and porosity of SPG membrane increased significantly due to the chemical corrosion caused by alkali NaClO solution used for online cleaning. Then the air permeation of SPG membrane was affected by membrane fouling and destroyed pore structure.

  5. Increase of intracellular cisplatin levels and radiosensitization by ultrasound in combination with microbubbles

    OpenAIRE

    Lammertink, Bart H A; Bos, Clemens; van der Wurff-Jacobs, Kim M; Storm, G; Moonen, Chrit T; Deckers, RHR

    2016-01-01

    The possibility to enhance drug delivery by using ultrasound in combination with microbubbles (USMB) is extensively studied. So far, these studies have focused on the delivery and efficacy of a single drug, e.g. in chemotherapy. In this study, we investigated the intracellular delivery of cisplatin by USMB and the subsequent increased efficacy in combination with radiotherapy in a head and neck cancer cell line in vitro. After USMB-mediated intracellular delivery was verified using the model-...

  6. Ultrasound-microbubble mediated cavitation of plant cells: effects on morphology and viability.

    Science.gov (United States)

    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 (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.

  7. Impact of microbubble enhanced, pulsed, focused ultrasound on tumor circulation of subcutaneous VX2 cancer

    Institute of Scientific and Technical Information of China (English)

    Li Peijing; Zhu Mei; Xu Yali; Zhao Yang; Gao Shunji; Liu Zheng; Gao Yun-hua

    2014-01-01

    Background Intravascular microbubble-enhanced acoustic cavitation is capable of disrupting the vascular walls of capillaries and small vessels.This study was designed to investigate the impact of microbubble-enhanced,pulsed and focused ultrasound (MEUS) on the blood perfusion of subcutaneous VX2 tumors in rabbits.Methods Subcutaneous VX2 cancers in twenty New Zealand rabbits were treated by combining high-pressure amplitude,pulsed and focused therapeutic ultrasound (TUS) and intravenous microbubble injections.The TUS transducer was operated with a peak negative pressure of 4.6 MPa and a duty cycle of 0.41%.Controls were subcutaneous VX2 cancers treated with TUS or microbubbles only.Contrast-enhanced ultrasound (CEUS) and intravenous Evans Blue (EB) perfusion were performed to assess the tumor circulation.The tumor microvascular disruption was assessed by histological examination.Results CEUS showed that the tumor circulation almost vanished after MEUS treatment.The average peak grayscale value (GSV) of tumor CEUS dropped significantly from 84.1±22.4 to 15.8±10.8 in the MEUS-treated tumors but no significant GSV changes were found in tumors in the two control groups.The mean tumor EB content of the MEUS-treated tumors was significantly lower than that of the controls.Histological examination found scattered tumor microvascular disruption with intercellular edema after MEUS treatment.Conclusion The tumor circulation of VX2 cancers can be arrested or significantly reduced by MEUS due to microvascular disruption.

  8. Quantifying synergistic mutual information

    CERN Document Server

    Griffith, Virgil

    2012-01-01

    Quantifying cooperation among random variables in predicting a single target random variable is an important problem in many biological systems with 10s to 1000s of co-dependent variables. We review the prior literature of information theoretical measures of synergy and introduce a novel synergy measure, entitled *synergistic mutual information* and compare it against the three existing measures of cooperation. We apply all four measures against a suite of binary circuits to demonstrate our measure alone quantifies the intuitive concept of synergy across all examples.

  9. Is Time Predictability Quantifiable?

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2012-01-01

    -case execution time. To compare different approaches we would like to quantify time predictability. That means we need to measure time predictability. In this paper we discuss the different approaches for these measurements and conclude that time predictability is practically not quantifiable. We can only......Computer architects and researchers in the realtime domain start to investigate processors and architectures optimized for real-time systems. Optimized for real-time systems means time predictable, i.e., architectures where it is possible to statically derive a tight bound of the worst...... compare the worst-case execution time bounds of different architectures....

  10. Observation of flow variation in capillaries of artificial blood vessel by producing microbubble aggregations.

    Science.gov (United States)

    Masuda, Kohji; Shigehara, Nobuhiko; Koda, Ren; Watarai, Nobuyuki; Ikeda, Seiichi; Arai, Fumihito; Miyamoto, Yoshitaka; Chiba, Toshio

    2012-01-01

    Microbubbles form their aggregations between the neighboring microbubbles by the effect of secondary Bjerknes force under ultrasound exposure. However, because of the difficulty to reproduce a capillary-mimicking artificial blood vessel, the behavior of aggregations in a capillary has not been predicted. Thus we prepared artificial blood vessels including a capillary model, which was made of poly(vinyl alcohol) (PVA) by grayscale lithography method, with minimum diameter of the path of 0.5 mm. By using this model we investigated the possibility of artificial embolization, where the microbubble aggregations might block entire vessels not to penetrate flow in downstream. Confirming that the sizes of flown aggregation were greater than the section area of the minimum path in the capillary model, we investigated the probability of path block in it. As the results we confirmed the probability increased in proportion to sound pressure and inversely to flow velocity. We are going to investigate with more kinds of parameters to enhance the possibility of artificial embolization.

  11. Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles.

    Science.gov (United States)

    Eggen, Siv; Fagerland, Stein-Martin; Mørch, Ýrr; Hansen, Rune; Søvik, Kishia; Berg, Sigrid; Furu, Håkon; Bøhn, Audun Dybvik; Lilledahl, Magnus B; Angelsen, Anders; Angelsen, Bjørn; de Lange Davies, Catharina

    2014-08-10

    The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation steps, and the interaction between sound waves and microbubbles generates biological effects that can be beneficial for the successful delivery of nanocarriers and their contents. In this study, a novel platform consisting of nanoparticle-stabilized microbubbles has been investigated for its potential for ultrasound-enhanced delivery to tumor xenografts. Confocal laser scanning microscopy was used to study the supply of nanoparticles from the vasculature and to evaluate the effect of different ultrasound parameters at a microscopic level. The results demonstrated that although the delivery is heterogeneous within tumors, there is a significant improvement in the delivery and the microscopic distribution of both nanoparticles and a released model drug when the nanoparticles are combined with microbubbles and ultrasound. The mechanisms that underlie the improved delivery are discussed.

  12. Obstructive Effects of Ultrasonic Microbubble Intensifier on CHG-5 Cell with Survivin Antisense Oligonucleotides Transfection

    Institute of Scientific and Technical Information of China (English)

    CAO Hong-ying; CAO You-de; WANG Zhi-gang; LI Pan

    2008-01-01

    Objective:To study the effects on human glioma cell line CHG-5 by ultrasonic microbubble intensifier with survivin antisense oligonucleotides (ASODN)transfection. Methods: Antisense oligonucleotides targeting survivin mRNA was designed and synthesized.Four regimen groups were designed,group A:survivin antisense oligonucleotides transfected with ultrasonic microbubble intensifier combined with ultrasound irradiation,group B: survivin antisense oligonucleotides transfected with lipofectamine combined with ultrasound irradiation,group C:survivin antisense oligonucelotides with lipofectamine transfection.group D:blank control.The expression changes of surviving protein were measured by immunohistochemical staining and Western blotting,and MTr assay was used to measure the changes of proliferation.Results:Survivin protein expression in group A was decreased significantly in human glioma cell line CHG-5 than other groups(P<0.05),and the proliferating rate of CHG-5 in group A was also significantly inhibited(P<0.05).Conclusion:Ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is a promising method in gene transfection effectively and noninvasively.

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

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    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)

  14. Real-time ultrasound brain perfusion imaging with analysis of microbubble replenishment in acute MCA stroke.

    Science.gov (United States)

    Kern, Rolf; Diels, Anna; Pettenpohl, Johanna; Kablau, Micha; Brade, Joachim; Hennerici, Michael G; Meairs, Stephen

    2011-08-01

    Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2 ± 13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58 ± 0.40 versus 1.25 ± 0.83; P=0.001; A=1.44 ± 1.75 versus 2.63 ± 2.31; P=0.05; A × β=1.14 ± 2.25 versus 2.98 ± 2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43 ± 2.67 versus 8.88 ± 1.66 seconds; Preplenishment correctly identifies ischemic brain tissue in acute MCA stroke.

  15. Experimental Study of Active Path Block in a Multi-Bifurcated Flow by Microbubble Aggregation

    Science.gov (United States)

    Shigehara, Nobuhiko; Demachi, Fumi; Koda, Ren; Mochizuki, Takashi; Masuda, Kohji; Ikeda, Seiichi; Arai, Fumihito; Miyamoto, Yoshitaka; Chiba, Toshio

    2013-07-01

    We previously reported our attempts at the active control of microbubble aggregations using acoustic radiation force, which propels microbubbles and adjusts the size of aggregations. However, because we used simple-shape artificial blood vessels, the behavior of aggregations in a small channel, e.g., the probability to obstruct the bloodstream, and the possibility of embolization, has not been predicted. Thus, we designed and fabricated a multi-bifurcated artificial blood vessel to apply to the production and active control of microbubble aggregations. Then, we introduced two kinds of ultrasound transducers for producing and propelling aggregations. First, we produced aggregations in a flow to measure their size and investigate their variation according to the emission duration of ultrasound. Then, we control the aggregations in an artificial blood vessel to verify their controllability. When ultrasound was stopped, the aggregations flaked off the vessel wall and flowed downstream, were propelled to the desired path, and finally were caught at a narrow path. We verified the same experiment under similar parameters to calculate the probability of realizing a path block. When the flow velocity was 20 mm/s, almost 50% of the aggregations were induced to flow through the desired path and a maximum probability of realizing a path block of 86% was achieved with the formation of aggregations.

  16. Quantitative ultrasound for the monitoring of novel microbubble and ultrasound radiosensitization.

    Science.gov (United States)

    Lee, Justin; Karshafian, Raffi; Papanicolau, Naum; Giles, Anoja; Kolios, Michael C; Czarnota, Gregory J

    2012-07-01

    There is a need for cancer imaging to provide "real-time" information about the metabolic and cellular responses of tumours. Quantitative ultrasound techniques have recently been demonstrated to be a potential method of assessing tumour response at the cellular level. Anti-cancer treatments administered to xenograft-bearing mice consisted of radiotherapy and a novel antivascular therapy utilizing encapsulated microbubble agents in the presence of ultrasound. Radiation dose and microbubble concentrations were varied and the treatment modalities were given in combination to assess the possible enhancement of tumour cell death. Quantitative methods were used to non-invasively assess responses. Results demonstrated statistically significant changes in backscatter parameters (midband fit, spectral intercept) in tumours treated with high doses of radiotherapy or a high concentration of microbubbles. Combined treatments demonstrated further increases in ultrasound parameters. Histopathologic assessment was used and tumour cell death was found to correlate with increases in ultrasound parameters. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. Use of Nonlinear Frequency Modulated Signals for the Enhancement of Subharmonic Response from Contrast Microbubbles

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    MUHAMMAD ARIF

    2017-01-01

    Full Text Available Ultrasound imaging with the subharmonic component from contrast microbubbles provide improved CTR (Contrast-to-Tissue Ratio, however it is susceptible to the low amplitude of the subharmonic component. In this simulation study, NLFM (Nonlinear Frequency Modulated signals are proposed in order to enhance the subharmonic response from microbubbles. NLFM signals having fractional bandwidths of 10, 20, and 40% with up and down sweeps were used as excitation. The performance of NLFM signals were compared with the reference tone-burst and LFM (Linear Frequency Modulated signals. The results show that the ultrasound contrast microbubbles can produce subharmonic response which is dependent on the applied signal pressure and bandwidth. It is observed that the subharmonic component of the scattered NLFM signal is 3.2dB higher than the LFM signal, whereas it is 9dB higher compared to the sinusoidal tone-burst signal. The results are also presented which show that the up and down sweeps NLFM signals performed better than the LFM signals at the same acoustic pressure and bandwidth.

  18. Enhancement of subharmonic emission from encapsulated microbubbles by using a chirp excitation technique.

    Science.gov (United States)

    Zhang, Dong; Gong, Yanjun; Gong, Xiufen; Liu, Zheng; Tan, Kaibin; Zheng, Hairong

    2007-09-21

    Subharmonic contrast imaging promises to improve ultrasound-imaging quality by taking advantage of an increased contrast to tissue signal. However, acoustic pressures beyond the subharmonic generation threshold using common ultrasound pulses may induce significant contrast microbubble destruction. In this work, a chirp excitation technique is presented to enhance the subharmonic emission from encapsulated microbubbles. Chirp signals with a center frequency of 5 MHz, variable frequency range and duration time are employed to drive microbubbles in numerical simulation and experimental studies. We provide a theoretical evaluation of the chirp excitation pressure threshold and the acoustic pressure dependence of subharmonic based on Church's model and demonstrate that the amplitude and axial resolution of the subharmonic can be optimized by proper selection of the frequency range and time duration of the chirp signal. Measurements are qualitatively in agreement with the simulation. Moreover, we demonstrate that chirp excitation may be able to improve the amplitude of the subharmonic component up to 22 dB over the pulse excitation. The chirp excitation technique could potentially be used for improving the subharmonic contrast imaging quality.

  19. Microbubble-Mediated Ultrasound Enhances the Lethal Effect of Gentamicin on Planktonic Escherichia coli

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    Han-Xiao Zhu

    2014-01-01

    Full Text Available Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922 was distributed to four different interventions: control (GCON, microbubble only (GMB, ultrasound only (GUS, and microbubble-mediated ultrasound (GMUS. Ultrasound was applied with 100 mW/cm2 (average intensity and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P<0.01. The minimal inhibitory concentration (MIC of gentamicin against E. coli was 1 μg/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 μg/mL. Transmission electron microscopy (TEM images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

  20. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    Science.gov (United States)

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue.

  1. A new method for quantifying and modeling large scale surface water inundation dynamics and key drivers using multiple time series of Earth observation and river flow data. A case study for Australia's Murray-Darling Basin

    Science.gov (United States)

    Heimhuber, Valentin; Tulbure, Mirela G.; Broich, Mark

    2017-04-01

    Periodically inundated surface water (SW) areas such as floodplains are hotspots of biodiversity and provide a broad range of ecosystem services but have suffered alarming declines in recent history. Large scale flooding events govern the dynamics of these areas and are a critical component of the terrestrial water cycle, but their propagation through river systems and the corresponding long term SW dynamics remain poorly quantified on continental or global scales. In this research, we used an unprecedented Landsat-based time series of SW maps (1986-2011), to develop statistical inundation models and quantify the role of driver variables across the Murray-Darling Basin (MDB) (1 million square-km), which is Australia's bread basket and subject to competing demands over limited water resources. We fitted generalized additive models (GAM) between SW extent as the dependent variable and river flow data from 68 gauges, spatial time series of rainfall (P; interpolated gauge data), evapotranspiration (ET; AWRA-L land surface model) and soil moisture (SM; active passive microwave satellite remote sensing) as predictor variables. We used a fully directed and connected river network (Australian Geofabric) in combination with ancillary data, to develop a spatial modeling framework consisting of 18,521 individual modeling units. We then fitted individual models for all modeling units, which were made up of 10x10 km grid cells split into floodplain, floodplain-lake and non-floodplain areas, depending on the type of water body and its hydrologic connectivity to a gauged river. We applied the framework to quantify flood propagation times for all major river and floodplain systems across the MDB, which were in good accordance with observed travel times. After incorporating these flow lag times into the models, average goodness of fit was high across floodplains and floodplain-lake modeling units (r-squared > 0.65), which were primarily driven by river flow, and lower for non

  2. Effect of acoustic parameters on the cavitation behavior of SonoVue microbubbles induced by pulsed ultrasound.

    Science.gov (United States)

    Lin, Yutong; Lin, Lizhou; Cheng, Mouwen; Jin, Lifang; Du, Lianfang; Han, Tao; Xu, Lin; Yu, Alfred C H; Qin, Peng

    2017-03-01

    SonoVue microbubbles could serve as artificial nuclei for ultrasound-triggered stable and inertial cavitation, resulting in beneficial biological effects for future therapeutic applications. To optimize and control the use of the cavitation of SonoVue bubbles in therapy while ensuring safety, it is important to comprehensively understand the relationship between the acoustic parameters and the cavitation behavior of the SonoVue bubbles. An agarose-gel tissue phantom was fabricated to hold the SonoVue bubble suspension. 1-MHz transmitting transducer calibrated by a hydrophone was used to trigger the cavitation of SonoVue bubbles under different ultrasonic parameters (i.e., peak rarefactional pressure (PRP), pulse repetition frequency (PRF), and pulse duration (PD)). Another 7.5-MHz focused transducer was employed to passively receive acoustic signals from the exposed bubbles. The ultraharmonics and broadband intensities in the acoustic emission spectra were measured to quantify the extent of stable and inertial cavitation of SonoVue bubbles, respectively. We found that the onset of both stable and inertial cavitation exhibited a strong dependence on the PRP and PD and a relatively weak dependence on the PRF. Approximate 0.25MPa PRP with more than 20μs PD was considered to be necessary for ultraharmonics emission of SonoVue bubbles, and obvious broadband signals started to appear when the PRP exceeded 0.40MPa. Moreover, the doses of stable and inertial cavitation varied with the PRP. The stable cavitation dose initially increased with increasing PRP, and then decreased rapidly after 0.5MPa. By contrast, the inertial cavitation dose continuously increased with increasing PRP. Finally, the doses of both stable and inertial cavitation were positively correlated with PRF and PD. These results could provide instructive information for optimizing future therapeutic applications of SonoVue bubbles.

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

    Directory of Open Access Journals (Sweden)

    Ibsen S

    2013-05-01

    Full Text Available Stuart Ibsen,1 Carolyn E Schutt,2 Sadik Esener31Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA; 2Department of Bioengineering, University of California at San Diego, La Jolla, CA, USA; 3Department of Nanoengineering, Moores Cancer Center, University of California at San Diego, La Jolla, CA, USAAbstract: 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

  4. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood-brain barrier.

    Science.gov (United States)

    Wang, Xiang; Liu, Ping; Yang, Weixiao; Li, Lu; Li, Peijing; Liu, Zheng; Zhuo, Zhongxiong; Gao, Yunhua

    2014-01-01

    Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%± 0.86%, and their size (2.64 ± 0.93 μm in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood-brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3 ± 2.4 μg/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6 ± 2.2 μg/g) > MTX alone (6.97 ± 0.75 μg/g) > MTX-liposome-coupled microbubbles (2.92 ± 0.39 μg/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (Pliposome-coupled microbubbles may hold great promise as new and effective therapies for primary central nervous system lymphoma and other central nervous system malignancies.

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

    Science.gov (United States)

    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.

  6. The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55).

    Science.gov (United States)

    Bzyl, Jessica; Palmowski, Moritz; Rix, Anne; Arns, Susanne; Hyvelin, Jean-Marc; Pochon, Sibylle; Ehling, Josef; Schrading, Simone; Kiessling, Fabian; Lederle, Wiltrud

    2013-02-01

    Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles. MCF-7 breast cancer xenografts were orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm(3) (2 mm diameter) up to 65 mm(3) (5 mm diameter) were examined with automated 3D molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles (BR55). Additionally, the relative tumour blood volume was assessed with non-targeted microbubbles (BR38). In vivo ultrasound data were validated by quantitative immunohistochemistry. Very small lesions 2 mm in diameter showed the highest binding of VEGFR2-specific microbubbles. In larger tumours significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2-targeted microbubbles was still high enough for imaging. The relative blood volume was comparable at all tumour sizes. Both findings were confirmed by immunohistochemistry. Additionally, a significantly enhanced number of large and mature vessels were detected with increasing tumour size (p < 0.01), explaining the decrease in VEGFR2 expression during tumour growth. 3D molecular ultrasound using BR55 is very well suited to depicting the angiogenic activity in very small breast lesions, suggesting its potential for detecting and characterising these lesions.

  7. Acoustic characterization and contrast imaging of microbubbles encapsulated by polymeric shells coated or filled with magnetic nanoparticles.

    Science.gov (United States)

    Sciallero, Claudia; Grishenkov, Dmitry; Kothapalli, Satya V V N; Oddo, Letizia; Trucco, Andrea

    2013-11-01

    The combination of superparamagnetic iron oxide nanoparticles with polymeric air-filled microbubbles is used to produce two types of multimodal contrast agents to enhance medical ultrasound and magnetic resonance imaging. The nanoparticles are either covalently linked to the shell or physically entrapped into the shell. In this paper, the characterization of the acoustic properties (backscattered power, fracturing pressure, attenuation and dispersion of the ultrasonic wave) and ultrasound imaging of the two types of magnetic microbubbles are presented. In vitro B-mode images are generated using a medical ultrasound scanner by applying a nonconventional signal processing technique that is suitable to detect polymeric bubbles and based on the combination of multipulse excitation and chirp coding. Even if both types of microbubbles can be considered to be effective ultrasound contrast agents, the different structure of the shell loaded with nanoparticles has a pronounced effect on the echogenicity and the detection sensitivity of the imaging technique. The best results are obtained using microbubbles that are externally coated with nanoparticles. A backscattered power of 20 dB was achieved at lower concentration, and an increment of 8 dB in the contrast-to-tissue ratio was observed with respect to the more rigid microbubbles with particles entrapped into the shell.

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

    Science.gov (United States)

    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.

  9. Docetaxel-loaded lipid microbubbles combined with ultrasound-triggered microbubble destruction for targeted tumor therapy in MHCC-H cells

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    Zhang Y

    2016-08-01

    Full Text Available Yue Zhang,1,* Ruijiao Chang,1,* Muqiong Li,2,* Kun Zhao,3 Hongzhi Zheng,4 Xiaodong Zhou1 1Department of Ultrasound, Xijing Hospital, 2Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an, 3Department of Cardiothoracic Surgery, The Third Chinese People’s Liberation Army Hospital, Baoji, Shaanxi Province, 4Department of Ultrasound, The 534 Hospital, Luoyang, Henan Province, People’s Republic of China *These authors contributed equally to this work Background: Efficient and targeted delivery of cytotoxic drugs is still a challenge in the fight against cancer. Ultrasound-targeted destruction of cytotoxic drug-loaded lipid microbubbles (LMs might be a promising method. This study aimed to explore the antitumor effects of docetaxel-loaded LM (DLLM combined with ultrasound-targeted microbubble destruction (UTMD on liver cancer. Materials and methods: DLLMs were made by a mechanical vibration technique. The effects of docetaxel, DLLM alone, and DLLM + UTMD on cell viability and cell proliferation (Cell Counting Kit-8 assay of MHCC-H cells and HepG2 cells were tested. The effects on cell cycle (flow cytometry and apoptosis (flow cytometry and immunoblotting of MHCC-H cells were tested. Solid fast-growing tumor mouse models were established and were randomized to blank LM + UTMD (controls or DLLM + UTMD. Tumor volume was compared between the two groups. Results: DLLMs had an 18%±7% drug-loading capacity, an 80%±3% encapsulation efficiency, and a mean particle size of 2,845 nm (75% range 1,527–5,534 nm. Compared to the other groups, DLLM + UTMD decreased the proliferation and increased the apoptosis of MHCC-H cells. DLLM + UTMD resulted in the inhibition of a higher proportion of cells in the G1 phase. Compared to the control group, the tumor volume in mice receiving DLLM + UTMD was smaller. Conclusion: DLLM + UTMD can increase the proportion of cells arrested in the G1 phase, decrease tumor cell proliferation

  10. Ultrasound Microbubbles Enhance the Neuroprotective Effect of Mouse Nerve Growth Factor on Intraocular Hypertension-Induced Neuroretina Damage in Rabbits

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    Xiaoli Shen

    2016-01-01

    Full Text Available Ultrasound microbubble combined optic protection drugs have obvious protective effect on optic nerve damage. This way of targeting drug delivery is becoming more simple, not through the whole body metabolism, avoiding drug via blood circulation when facing the decomposition and the environment in the interference and destruction process of drugs, to maximize the guarantee to reach target organs of drug concentration and to reache the maximum therapeutic effect. The technique of ultrasound microbubbles is safe, controllable, nonimmunogenic, and repeatable. It provides us with a novel idea in the administration of neuroprotective drugs.

  11. The influence of acoustic transmit parameters on the destruction of contrast microbubbles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Shi, William T [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Forsberg, Flemming [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Vaidyanathan, Priya [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Tornes, Audun [GE Healthcare, Oslo (Norway); Oestensen, Jonny [GE Healthcare, Oslo (Norway); Goldberg, Barry B [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2006-08-21

    In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz), acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (p {<=} 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

  12. Quantitative ultrasound characterization of tumor cell death: ultrasound-stimulated microbubbles for radiation enhancement.

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    Hyunjung Christina Kim

    Full Text Available The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy. In parallel, in situ end-labelling (ISEL staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

  13. Targeted and reversible blood-retinal barrier disruption via focused ultrasound and microbubbles.

    Directory of Open Access Journals (Sweden)

    Juyoung Park

    Full Text Available The blood-retinal barrier (BRB prevents most systemically-administered drugs from reaching the retina. This study investigated whether burst ultrasound applied with a circulating microbubble agent can disrupt the BRB, providing a noninvasive method for the targeted delivery of systemically administered drugs to the retina. To demonstrate the efficacy and reversibility of such a procedure, five overlapping targets around the optic nerve head were sonicated through the cornea and lens in 20 healthy male Sprague-Dawley rats using a 690 kHz focused ultrasound transducer. For BRB disruption, 10 ms bursts were applied at 1 Hz for 60 s with different peak rarefactional pressure amplitudes (0.81, 0.88 and 1.1 MPa. Each sonication was combined with an IV injection of a microbubble ultrasound contrast agent (Definity. To evaluate BRB disruption, an MRI contrast agent (Magnevist was injected IV immediately after the last sonication, and serial T1-weighted MR images were acquired up to 30 minutes. MRI contrast enhancement into the vitreous humor near targeted area was observed for all tested pressure amplitudes, with more signal enhancement evident at the highest pressure amplitude. At 0.81 MPa, BRB disruption was not detected 3 h post sonication, after an additional MRI contrast injection. A day after sonication, the eyes were processed for histology of the retina. At the two lower exposure levels (0.81 and 0.88 MPa, most of the sonicated regions were indistinguishable from the control eyes, although a few tiny clusters of extravasated erythrocytes (petechaie were observed. More severe retinal damage was observed at 1.1 MPa. These results demonstrate that focused ultrasound and microbubbles can offer a noninvasive and targeted means to transiently disrupt the BRB for ocular drug delivery.

  14. Production of microbubbles from axisymmetric flow focusing in the jetting regime for moderate Reynolds numbers.

    Science.gov (United States)

    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.

  15. Resonance Frequency of Optical Microbubble Resonators: Direct Measurements and Mitigation of Fluctuations

    Science.gov (United States)

    Cosci, Alessandro; Berneschi, Simone; Giannetti, Ambra; Farnesi, Daniele; Cosi, Franco; Baldini, Francesco; Nunzi Conti, Gualtiero; Soria, Silvia; Barucci, Andrea; Righini, Giancarlo; Pelli, Stefano

    2016-01-01

    This work shows the improvements in the sensing capabilities and precision of an Optical Microbubble Resonator due to the introduction of an encaging poly(methyl methacrylate) (PMMA) box. A frequency fluctuation parameter σ was defined as a score of resonance stability and was evaluated in the presence and absence of the encaging system and in the case of air- or water-filling of the cavity. Furthermore, the noise interference introduced by the peristaltic and the syringe pumping system was studied. The measurements showed a reduction of σ in the presence of the encaging PMMA box and when the syringe pump was used as flowing system. PMID:27589761

  16. Microscopic study of ultrasound-mediated microbubble destruction effects on vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Yi-Rong Hou; Tian Chen; Bing Hu

    2015-01-01

    Objective: To observe vascular smooth muscle cell morphological changes induced by ultrasound combined with microbubbles by Atomic Force Acoustic Microscopy (AFAM). Methods: A7r5 rat aortic smooth muscle cells were divided into groups: control group (without ultrasonic irradiation, no micro bubbles) and US+MB group (45 kHz, 0.4 W/cm2 ultrasound irradiate for 20 seconds with a SonoVue™ concentration of [(56-140)×10 5/mL]. Cell micro-morphological changes (such as topographic and acoustic prognosis) were detected, before and after ultrasound destruction by AFAM. Results: In cell morphology, smooth muscle cells were spread o and connected to each another by fibers. At the center of the cell, the nuclear area had a rough surface and was significantly elevated from its surroundings. The cytoskeletal structure of the reticular nucleus and cytoplasm in the morphology of A7r5 cells (20μm×20μm) were clear before microbubble intervention. After acoustic exciting, the cell structure details of the acoustic image were improved with better resolution, showing the elasticity of different tissues. In the acoustic image, the nucleus was harder, more flexible and uneven compared with the cytoplasm. Many strong various-sized echo particles were stuck on the rough nuclear membrane’s substrate surface. The nuclear membrane did not have a continuous smooth surface; there were many obstructions (pores). After ultrasound-intervention was combined with microbubbles, the dark areas of the A7r5 cell images was increased in various sizes and degrees. The dark areas showed the depth or low altitudes of the lower regions, suggesting regional depressions. However, the location and scope of the acoustic image dark areas were not similar to those found in the topographic images. Therefore, it was likely that the dark areas, both from the topographic and acoustic images, were sound-holes. In addition, some cell nuclei become round in different degrees after irradiation. Conclusions: Atomic

  17. Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System.

    Science.gov (United States)

    Burgess, Alison; Hynynen, Kullervo

    2016-01-01

    The blood-brain barrier is a serious impediment to the delivery of pharmaceutical treatments for brain diseases, including cancer, neurodegenerative and neuropsychatric diseases. Focused ultrasound, when combined with microbubbles, has emerged as an effective method to transiently and locally open the blood-brain barrier to promote drug delivery to the brain. Focused ultrasound has been used to successfully deliver a wide variety of therapeutic agents to pre-clinical disease models. The requirement for clinical translation of focused ultrasound technology is considered.

  18. On Quantifying Semantic Information

    Directory of Open Access Journals (Sweden)

    Simon D’Alfonso

    2011-01-01

    Full Text Available The purpose of this paper is to look at some existing methods of semantic information quantification and suggest some alternatives. It begins with an outline of Bar-Hillel and Carnap’s theory of semantic information before going on to look at Floridi’s theory of strongly semantic information. The latter then serves to initiate an in-depth investigation into the idea of utilising the notion of truthlikeness to quantify semantic information. Firstly, a couple of approaches to measure truthlikeness are drawn from the literature and explored, with a focus on their applicability to semantic information quantification. Secondly, a similar but new approach to measure truthlikeness/information is presented and some supplementary points are made.

  19. 孤立性肺腺癌血流模式定量CT参数相互关系%Correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Shenjiang Li; Xiangsheng Xiao; Shiyuan Liu; Huimin Li; Chengzhou Li; Chenshi Zhang

    2007-01-01

    Objective: To evaluate the correlation of the quantifiable parameters of blood flow pattern derived with dynamic CT in solitary bronchogenic adenocarcinoma (SBA). Methods: 46 patients with solitary bronchogenic adenocarcinomas (SBA) (diameter ≤ 4 cm) underwent multi-location dynamic contrast material-enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 mL/s by using an autoinjector 90 mL, 4 × 5 mm or 4 × 2.5 mm scanning mode with stable table were performed) serial CT. Precontrast and postcontrast attenuation on every scan was recorded. Perfusion (PBA), peak height (PHBA), ratio of peak height of the SPN to that of the aorta (BA-to-A ratio) and mean transit time (MTT) were calculated. The correlation between peak height of the aorta (PHA) and parameters of the SBA (PHBA, BA-to-A ratio, PBA, and MTT) and those among parameters of the SBA were assessed by means of linear regression analysis. Regression equation among parameters of the SBA were obtain by means of stepwise regression. Results: The correlation between the SBA peak height (PHBA, 36.78 HU ± 12.02) and the aortic peak height (PHA) was significant (r = 0.506, P < 0.0001). No significant cor relation was found between the BA-to-A peak height ratio (15.33% ± 4.55) and the aortic peak height (r = 0.130, P = 0.388 >0.05) as it was between the SBA perfusion (PBA, 31.86 mL/min/100 g ± 9.74) and the aortic peak height (r = 0.049, P = 0.749 > 0.05). The SBA perfusion correlated with the PHBA and the BA-to-A peak height ratio (r = 0.394, P = 0.007 < 0.05; r = 0.407, P = 0.005 < 0.05). The PHBA correlated positively with the BA-to-A peak height ratio (r = 0.781, P < 0.0001). Mean transit time was 14.84 s ± 5.52. PBA = 18.500 + 0.872 × BA-to-A ratio. BA-to-A ratio = 4.467 + 0.295 × PHBA. Conclusion: The linear correlation between the SBA perfusion and BA-to-A ratio and that between BA-to-A ratio and PHBA can be expressed by equation.It is possible to

  20. Targeting accuracy and closing timeline of the microbubble-enhanced focused ultrasound blood-brain barrier opening in non-human primates

    Science.gov (United States)

    Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Wu, Shih-Ying; Wang, Shutao; Downs, Matthew; Ferrera, Vincent P.; Konofagou, Elisa E.

    2012-11-01

    The delivery of drugs to specific neural targets faces two fundamental problems: Most drugs do not cross the blood-brain barrier and those that do spread to all parts of the brain. To date there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in the non-human primate. Using this system for selective blood-brain barrier disruption is technically no more challenging than positioning a TMS coil, and does not rely on MRI-guided targeting or expensive phased array ultrasound systems. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. Here we tested the accuracy of the system by targeting the caudate nucleus of the basal ganglia in two macaque monkeys. Our results show that average in-plane error of the system is on the order of 2 mm and targeting error in depth, i.e., along the ultrasound path, is even smaller and averaged 1.2 mm. In summary, targeting accuracy of our system is good enough to enable the selective delivery of drugs to specific sub-structures of the basal ganglia.

  1. Improved Electricity Generation by a Microbial Fuel Cell after Pretreatment of Ammonium and Nitrate in Livestock Wastewater with Microbubbles and a Catalyst.

    Science.gov (United States)

    Jang, Jae Kyung; Kim, Taeyoung; Kang, Sukwon; Sung, Je Hoon; Kang, Youn Koo; Kim, Young Hwa

    2016-11-28

    Livestock wastewater containing high concentrations of ammonium and nitrate ions was pretreated with microbubbles and an Fe/MgO catalyst prior to its application in microbial fuel cells because high ion concentrations can interfere with current generation. Therefore, tests were designed to ascertain the effect of pretreatment on current generation. In initial tests, the optimal amount of catalyst was found to be 300 g/l. When 1,000 ml/min O₂ was used as the oxidant, the removal of ammonium- and nitrate-nitrogen was highest. After the operating parameters were optimized, the removal of ammonium and nitrate ions was quantified. The maximum ammonium removal was 32.8%, and nitrate was removed by up to 75.8% at a 500 g/l catalyst concentration over the course of the 2 h reaction time. The current was about 0.5 mA when livestock wastewater was used without pretreatment, whereas the current increased to 2.14 ± 0.08 mA when livestock wastewater was pretreated with the method described above. This finding demonstrates that a 4-fold increase in the current can be achieved when using pretreated livestock wastewater. The maximum power density and current density performance were 10.3 W/m³ and 67.5 A/m³, respectively, during the evaluation of the microbial fuel cells driven by pretreated livestock wastewater.

  2. Development of a new therapeutic technique to direct stem cells to the infarcted heart using targeted microbubbles: StemBells

    NARCIS (Netherlands)

    L. Woudstra; P.A.J. Krijnen (Paul); S.J.P. Bogaards; E. Meinster; R.W. Emmens; T.J.A. Kokhuis (Tom); I.A.E. Bollen; H. Baltzer; S.M.T. Baart; R. Parbhudayal; K. Helder MScN (Onno); V.W.M. van Hinsbergh (Victor); R.J.P. Musters (René); N. de Jong (Nico); O. Kamp (Otto); H.W.M. Niessen (Hans ); A. van Dijk (Annemieke); L.J.M. Juffermans (Lynda)

    2016-01-01

    textabstractSuccessful stem cell therapy after acute myocardial infarction (AMI) is hindered by lack of engraftment of sufficient stem cells at the site of injury. We designed a novel technique to overcome this problem by assembling stem cell-microbubble complexes, named 'StemBells'.StemBells were a

  3. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    Science.gov (United States)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  4. Soft X-ray induced modifications of PVA-based microbubbles in aqueous environment: a microspectroscopy study.

    Science.gov (United States)

    Tzvetkov, George; Fernandes, Paulo; Wenzel, Stephan; Fery, Andreas; Paradossi, Gaio; Fink, Rainer H

    2009-02-21

    We use scanning-transmission X-ray microspectroscopy (STXM) for in situ characterization of the physicochemical changes in air-filled poly(vinyl alcohol) (PVA) based microbubbles upon soft X-ray irradiation. The microbubbles were illuminated directly in aqueous suspension with 520 eV X-rays and a continuous shrinkage of the particles with an illumination time/radiation dose was observed. Utilizing the intrinsic absorption properties of the species and the high spatial resolution of the STXM, the modifications of the particles' structure were simultaneously recognized. A thorough characterization of the microbubble volume, membrane thickness and absorption coefficient was performed by quantitative fitting of the radial transmittance profiles of the targeted microbubbles. Apart from the observed volume contraction, there was no significant change in the shell thickness. The chemical changes in the membranes were clarified via C K-edge near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. It was revealed that the observed structural alterations go along with a continuous degradation of the PVA network associated with formation of carbonyl- and carboxyl-containing species as well as an increased content of unsaturated bonds.

  5. Quantifying economic fluctuations

    Science.gov (United States)

    Stanley, H. Eugene; Nunes Amaral, Luis A.; Gabaix, Xavier; Gopikrishnan, Parameswaran; Plerou, Vasiliki

    2001-12-01

    This manuscript is a brief summary of a talk designed to address the question of whether two of the pillars of the field of phase transitions and critical phenomena-scale invariance and universality-can be useful in guiding research on interpreting empirical data on economic fluctuations. Using this conceptual framework as a guide, we empirically quantify the relation between trading activity-measured by the number of transactions N-and the price change G( t) for a given stock, over a time interval [ t, t+Δ t]. We relate the time-dependent standard deviation of price changes-volatility-to two microscopic quantities: the number of transactions N( t) in Δ t and the variance W2( t) of the price changes for all transactions in Δ t. We find that the long-ranged volatility correlations are largely due to those of N. We then argue that the tail-exponent of the distribution of N is insufficient to account for the tail-exponent of P{ G> x}. Since N and W display only weak inter-dependency, our results show that the fat tails of the distribution P{ G> x} arises from W. Finally, we review recent work on quantifying collective behavior among stocks by applying the conceptual framework of random matrix theory (RMT). RMT makes predictions for “universal” properties that do not depend on the interactions between the elements comprising the system, and deviations from RMT provide clues regarding system-specific properties. We compare the statistics of the cross-correlation matrix C-whose elements Cij are the correlation coefficients of price fluctuations of stock i and j-against a random matrix having the same symmetry properties. It is found that RMT methods can distinguish random and non-random parts of C. The non-random part of C which deviates from RMT results, provides information regarding genuine collective behavior among stocks. We also discuss results that are reminiscent of phase transitions in spin systems, where the divergent behavior of the response function at

  6. Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin

    Science.gov (United States)

    Jetha, Sheliza; Karshafian, Raffi

    2017-03-01

    Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (pcancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.

  7. Combined perfusion and doppler imaging using plane-wave nonlinear detection and microbubble contrast agents.

    Science.gov (United States)

    Tremblay-Darveau, Charles; Williams, Ross; Milot, Laurent; Bruce, Matthew; Burns, Peter N

    2014-12-01

    Plane-wave imaging offers image acquisition rates at the pulse repetition frequency, effectively increasing the imaging frame rates by up to two orders of magnitude over conventional line-by-line imaging. This form of acquisition can be used to achieve very long ensemble lengths in nonlinear modes such as pulse inversion Doppler, which enables new imaging trade-offs that were previously unattainable. We first demonstrate in this paper that the coherence of microbubble signals under repeated exposure to acoustic pulses of low mechanical index can be as high as 204 ± 5 pulses, which is long enough to allow an accurate power Doppler measurement. We then show that external factors, such as tissue acceleration, restrict the detection of perfusion at the capillary level with linear Doppler, even if long Doppler ensembles are considered. Hence, perfusion at the capillary level can only be detected with ultrasound through combined microbubbles and Doppler imaging. Finally, plane-wave contrast-enhanced power and color Doppler are performed on a rabbit kidney in vivo as a proof of principle. We establish that long pulse-inversion Doppler sequences and conventional wall-filters can create an image that simultaneously resolves both the vascular morphology of veins and arteries, and perfusion at the capillary level with frame rates above 100 Hz.

  8. Ultrasound triggered image-guided drug delivery to inhibit vascular reconstruction via paclitaxel-loaded microbubbles.

    Science.gov (United States)

    Zhu, Xu; Guo, Jun; He, Cancan; Geng, Huaxiao; Yu, Gengsheng; Li, Jinqing; Zheng, Hairong; Ji, Xiaojuan; Yan, Fei

    2016-02-22

    Paclitaxel (PTX) has been recognized as a promising drug for intervention of vascular reconstructions. However, it is still difficult to achieve local drug delivery in a spatio-temporally controllable manner under real-time image guidance. Here, we introduce an ultrasound (US) triggered image-guided drug delivery approach to inhibit vascular reconstruction via paclitaxel (PTX)-loaded microbubbles (PLM) in a rabbit iliac balloon injury model. PLM was prepared through encapsulating PTX in the shell of lipid microbubbles via film hydration and mechanical vibration technique. Our results showed PLM could effectively deliver PTX when exposed to US irradiation and result in significantly lower viability of vascular smooth muscle cells. Ultrasonographic examinations revealed the US signals from PLM in the iliac artery were greatly increased after intravenous administration of PLM, making it possible to identify the restenosis regions of iliac artery. The in vivo anti-restenosis experiments with PLM and US greatly inhibited neointimal hyperplasia at the injured site, showing an increased lumen area and reduced the ratio of intima area and the media area (I/M ratio). No obvious functional damages to liver and kidney were observed for those animals. Our study provided a promising approach to realize US triggered image-guided PTX delivery for therapeutic applications against iliac restenosis.

  9. Investigation on the relationship between overpressure and sub-harmonic response from encapsulated microbubbles

    Science.gov (United States)

    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.

  10. Mechanism of Microbubble Growth at Mitral Mechanical Heart Valve (MHV) Closure

    Science.gov (United States)

    Rambod, Edmond; Beizaie, Masoud; Shusser, Michael; Gharib, Morteza

    1999-11-01

    The growth mechanism of microbubbles at mitral MHV closure has been experimentally studied. In the heart, some of the tiny bubbles grow explosively and form larger and persistent bubbles. An experimental set-up was designed to allow the passage of micron-size bubbles through an 80 micron-wide slot, simulating a typical gap between the housing ring and the occluders in MHV. The bubbles were generated using an air-liquid dispenser and were delivered to the system via a 250 micron-diameter hypedermic needle positioned vertically near the slot. A solenoid valve was used to deliver a 10cc volume of liquid in 25ms time through the slot. High-speed imaging was used to study the impact of flow through the slot on bubble growth. The velocity of liquid through the slot was assessed to be in the range of 12-15 m/s. Our observations confirmed the rapid and drastic growth of microbubbles following their passage through the narrow slot, due to pressure drop. Vortices, which were induced by flow separation on the downstream of the slot, caused the grown bubbles to shatter and form more stable bubbles.

  11. Augmentation of transgenic expression by ultrasound‑mediated liposome microbubble destruction.

    Science.gov (United States)

    Chen, Zhi-Yi; Sun, Xiao-Fang; Liu, Jian-Qiao; Si-Tu, Bing; Qiu, Ri-Xiang; Liang, Kun; Liu, Jian-Hua; Liang, Wei-Xiang; Zhou, Xin-Xin; Zhang, Hua; Yu, Jiang-Xiu

    2012-04-01

    Non-invasive, efficient and tissue-specific transgenic technologies could be valuable in gene therapy. Although non-viral carriers may be safer and cheaper, they have a much lower transfection efficiency than viral gene carriers. The present study was designed to test the transgenic expression and safety of red fluorescent protein (RFP) in HeLa cells in vitro and in transplanted tumors of nude mice in vivo under ultrasound-mediated liposome microbubble destruction (UMLMD) conditions. Plasmids containing RFP were gently mixed with liposome microbubbles (LMs). The mixture was added to HeLa cells or injected into BALB/c mice by the tail vein under various ultrasound exposure and LM parameters, and then the transfection efficiencies were examined. The results in vivo and in vitro demonstrated that, following a comparison of the plasmid group, the ultrasound + plasmid group and the LM + plasmid group, UMLMD significantly increased the transgenic expression (P<0.01) without causing any apparent detrimental effect. From the study, we concluded that UMLMD could be a non-invasive, effective and promising non-viral technique for gene therapy and transgenic research.

  12. Quantum-dot-modified microbubbles with bi-mode imaging capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Ke Hengte; Xing Zhanwen; Guo Caixin; Yue Xiuli; Liu Shaoqin; Dai Zhifei [Nanobiotechnology Division, Bio-X Center, State Key Laboratory of Urban Water Resources and Environment, Harbin Institute of Technology, Harbin 150001 (China); Zhao Bo; Wang Jinrui [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Liu Jibin [Ultrasound Research and Education Institute, Thomas Jefferson University Hospital, Philadelphia, PA 19107 (United States); Tang Zhiyong, E-mail: jinrui_wang@sina.co, E-mail: ji-bin.liu@jefferson.ed, E-mail: zhifei.dai@hit.edu.c [National Center of Nanoscience and Technology, Beijing 100190 (China)

    2009-10-21

    The aim of this paper was to develop a novel bi-mode ultrasound/fluorescent imaging agent through stepwise layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and CdTe quantum dots (QDs) onto ST68 microbubbles (MBs) produced by sonication of a mixture of surfactants (Span 60 and Tween 80). The experiments using photoluminescence spectroscopy and confocal laser scanning microscopy confirmed that CdTe nanoparticles were successfully adsorbed on the outer surface of the MBs. The static light scattering measurements showed that size distributions of MBs before and after QD deposition met the size requirements for clinical application. The in vitro and in vivo ultrasonography indicated that the QD-modified MBs maintained good contrast enhancement properties as the original MBs. Furthermore, the in vitro ultrasound-targeted microbubble destruction (UTMD) experiment of the QD-MB composites was carried out to validate the ability of MBs to deliver QDs for fluorescent imaging. The results showed that the QD-modified MBs not only maintained the capability of ultrasound imaging, but also could be used as a targeted-drug controlled-release system to deliver the QDs for cell and tissue fluorescent imaging by UTMD. The novel dual-functional imaging agent has potential for a variety of biological and medical applications.

  13. Quantum-dot-modified microbubbles with bi-mode imaging capabilities

    Science.gov (United States)

    Ke, Hengte; Xing, Zhanwen; Zhao, Bo; Wang, Jinrui; Liu, Jibin; Guo, Caixin; Yue, Xiuli; Liu, Shaoqin; Tang, Zhiyong; Dai, Zhifei

    2009-10-01

    The aim of this paper was to develop a novel bi-mode ultrasound/fluorescent imaging agent through stepwise layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and CdTe quantum dots (QDs) onto ST68 microbubbles (MBs) produced by sonication of a mixture of surfactants (Span 60 and Tween 80). The experiments using photoluminescence spectroscopy and confocal laser scanning microscopy confirmed that CdTe nanoparticles were successfully adsorbed on the outer surface of the MBs. The static light scattering measurements showed that size distributions of MBs before and after QD deposition met the size requirements for clinical application. The in vitro and in vivo ultrasonography indicated that the QD-modified MBs maintained good contrast enhancement properties as the original MBs. Furthermore, the in vitro ultrasound-targeted microbubble destruction (UTMD) experiment of the QD-MB composites was carried out to validate the ability of MBs to deliver QDs for fluorescent imaging. The results showed that the QD-modified MBs not only maintained the capability of ultrasound imaging, but also could be used as a targeted-drug controlled-release system to deliver the QDs for cell and tissue fluorescent imaging by UTMD. The novel dual-functional imaging agent has potential for a variety of biological and medical applications.

  14. BR1: A new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles

    Energy Technology Data Exchange (ETDEWEB)

    Scheider, M.; Arditi, M.; Barrau, M.B.

    1995-08-01

    Rationale and objectives. The basic characteristics of BR1, a novel echo contrast agent based on stabilized sulfur hexafluoride (SF{sub 6}) microbubbles have been evaluated. Methods. The authors determined the physicochemical properties (bubble concentration, bubble size distribution, resistance to pressure, and stability) and the acoustic properties (backscatter and attenuation coefficients) of BR1. The diagnostic value of BR1 was evaluated further in minipigs. Left heart images were recorded before and after injection of different doses of BR1. Results. BR1 is formulated as a lyophilized products, which after addition of saline, provides a suspension containing 2 X 10{sup 8} SF{sub 6} microbubbles/mL with a number mean diameter of 2.5 {mu}m. More than 90% of the bubbles are below 8 {mu}m. The use of SF{sub 6} rather than air provides an improved resistance to pressure increases such as the ones occuring in the left heart during systole. After reconstitution, the echogenicity and the bubble characteristics are unchanged for more than 8 hours. The high echogenicity remains almost constant over the entire medical frequency range (1-10 MH{sub Z}). BR1 injections in animals resulted in a homogenous, dose-dependent opacification of the left heart. Conclusions. Considering its high echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a very promising ultrasound contrast agent. 14 refs., 8 figs., 3 tabs.

  15. Reducing formation damage with microbubble based drilling fluid : understanding the blocking ability

    Energy Technology Data Exchange (ETDEWEB)

    Bjorndalen, N.; Kuru, E. [Alberta Univ., Edmonton, AB (Canada). School of Mining and Petroleum Engineering; Jossy, E.; Alvarez, J.M. [Alberta Research Council, Devon, AB (Canada)

    2007-07-01

    Micro-bubble based drilling fluids use gas bubbles to bridge pores in porous media. The microbubbles can be removed during the initial stages of production to reduce costs associated with stimulation processes. This paper provided details of experiments conducted to investigate pore blocking mechanisms. Micromodel cells were used with different pressure rates and fluid compositions. A xanthan gum-water mixture was used as a base drilling fluid. An anionic surfactant was added to the base fluid for aphronization. The resulting stable foam was injected into the micromodel, where it blocked porous media. The analysis demonstrated that an aphron of 60 {mu}m bubble will invade porous media with a pore diameter of 50 {mu} at approximately 10 kPa. The foam was effectively removed by water injection, which indicated that the effects of the foam were irreversible. Less fluid and surfactant was needed to achieve desired flow rates when the foam was used. It was concluded that drilling with aphronized fluid will reduce formation damage. Further research is required to determine maximum flow pressure of the aphronized fluid in porous media. 24 refs., 1 tab., 17 figs.

  16. In vitro characterization of the subharmonic ultrasound signal from Definity microbubbles at high frequencies.

    Science.gov (United States)

    Cheung, K; Couture, O; Bevan, P D; Cherin, E; Williams, R; Burns, P N; Foster, F S

    2008-03-07

    Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at one-half the driving frequency. At ultrasound frequencies in the 20-40 MHz range, the subharmonic offers the potential to differentiate the blood in the microcirculation from the surrounding tissue. It is unknown whether current contrast agents, manufactured to be resonant between 2 and 12 MHz, are ideal for subharmonic imaging at higher frequencies. We performed numerical simulations of the Keller-Miksis model for the behavior of a single bubble and experimental investigations of Definity microbubbles in water. The results supported the hypothesis that off-resonant bubbles, excited at their second harmonic, may be primarily responsible for the observed subharmonic energy. For frequencies between 20 and 32 MHz and 32 and 40 MHz, the optimal bubble diameters for the generation of subharmonics in vitro were determined experimentally to be 1.2-5 microm and less than 1.2 microm, respectively. Definity may be a suitable ultrasound contrast agent for subharmonic imaging at 20 MHz with peak-negative pressures between 380 and 590 kPa and pulses greater than or equal to four cycles in duration.

  17. Effects of encapsulation damping on the excitation threshold for subharmonic generation from contrast microbubbles.

    Science.gov (United States)

    Katiyar, Amit; Sarkar, Kausik

    2012-11-01

    A recent study [Katiyar and Sarkar (2011). J. Acoust. Soc. Am. 130, 3137-3147] showed that in contrast to the analytical result for free bubbles, the minimum threshold for subharmonic generation for contrast microbubbles does not necessarily occur at twice the resonance frequency. Here increased damping-either due to the small radius or the encapsulation-is shown to shift the minimum threshold away from twice the resonance frequency. Free bubbles as well as four models of the contrast agent encapsulation are investigated varying the surface dilatational viscosity. Encapsulation properties are determined using measured attenuation data for a commercial contrast agent. For sufficiently small damping, models predict two minima for the threshold curve-one at twice the resonance frequency being lower than the other at resonance frequency-in accord with the classical analytical result. However, increased damping damps the bubble response more at twice the resonance than at resonance, leading to a flattening of the threshold curve and a gradual shift of the absolute minimum from twice the resonance frequency toward the resonance frequency. The deviation from the classical result stems from the fact that the perturbation analysis employed to obtain it assumes small damping, not always applicable for contrast microbubbles.

  18. Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism-Induced Acute Ischemic Stroke.

    Science.gov (United States)

    Lu, Yongkang; Wang, Junfen; Huang, Ruizhu; Chen, Gangbin; Zhong, Lintao; Shen, Shuxin; Zhang, Chuanxi; Li, Xinzhong; Cao, Shiping; Liao, Wangjun; Liao, Yulin; Bin, Jianping

    2016-05-01

    Microthrombi originating from disintegrated clots or formed in situ may account for the poor clinical improvement of acute ischemic stroke after recanalization therapy. We attempted to determine whether microbubble-mediated sonothrombolysis could dissolve platelet-rich and erythrocyte-rich microthrombi, thereby reducing their brain injury-causing potential. Platelet- and erythrocyte-rich microthrombosis were induced by periadventitial application of 5% ferric chloride or thrombin to mesenteric microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by intracarotid injection of platelet- or erythrocyte-rich microthrombi in another 50 rats. Rats were randomly divided into control (CON), ultrasound (US), ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel recanalization rates, cerebral infarct volumes, and neurological scores were determined. The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (Pacute ischemic stroke. Thus, this method may serve as an attractive adjunct to recanalization therapy for acute ischemic stroke. © 2016 American Heart Association, Inc.

  19. Quantifying traffic exposure.

    Science.gov (United States)

    Pratt, Gregory C; Parson, Kris; Shinoda, Naomi; Lindgren, Paula; Dunlap, Sara; Yawn, Barbara; Wollan, Peter; Johnson, Jean

    2014-01-01

    Living near traffic adversely affects health outcomes. Traffic exposure metrics include distance to high-traffic roads, traffic volume on nearby roads, traffic within buffer distances, measured pollutant concentrations, land-use regression estimates of pollution concentrations, and others. We used Geographic Information System software to explore a new approach using traffic count data and a kernel density calculation to generate a traffic density surface with a resolution of 50 m. The density value in each cell reflects all the traffic on all the roads within the distance specified in the kernel density algorithm. The effect of a given roadway on the raster cell value depends on the amount of traffic on the road segment, its distance from the raster cell, and the form of the algorithm. We used a Gaussian algorithm in which traffic influence became insignificant beyond 300 m. This metric integrates the deleterious effects of traffic rather than focusing on one pollutant. The density surface can be used to impute exposure at any point, and it can be used to quantify integrated exposure along a global positioning system route. The traffic density calculation compares favorably with other metrics for assessing traffic exposure and can be used in a variety of applications.

  20. Quantifying loopy network architectures.

    Directory of Open Access Journals (Sweden)

    Eleni Katifori

    Full Text Available Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of approaches have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes from the metric topology (connectivity and edge weight and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.

  1. Uncertainty quantified trait predictions

    Science.gov (United States)

    Fazayeli, Farideh; Kattge, Jens; Banerjee, Arindam; Schrodt, Franziska; Reich, Peter

    2015-04-01

    Functional traits of organisms are key to understanding and predicting biodiversity and ecological change, which motivates continuous collection of traits and their integration into global databases. Such composite trait matrices are inherently sparse, severely limiting their usefulness for further analyses. On the other hand, traits are characterized by the phylogenetic trait signal, trait-trait correlations and environmental constraints, all of which provide information that could be used to statistically fill gaps. We propose the application of probabilistic models which, for the first time, utilize all three characteristics to fill gaps in trait databases and predict trait values at larger spatial scales. For this purpose we introduce BHPMF, a hierarchical Bayesian extension of Probabilistic Matrix Factorization (PMF). PMF is a machine learning technique which exploits the correlation structure of sparse matrices to impute missing entries. BHPMF additionally utilizes the taxonomic hierarchy for trait prediction. Implemented in the context of a Gibbs Sampler MCMC approach BHPMF provides uncertainty estimates for each trait prediction. We present comprehensive experimental results on the problem of plant trait prediction using the largest database of plant traits, where BHPMF shows strong empirical performance in uncertainty quantified trait prediction, outperforming the state-of-the-art based on point estimates. Further, we show that BHPMF is more accurate when it is confident, whereas the error is high when the uncertainty is high.

  2. Quantifying innovation in surgery.

    Science.gov (United States)

    Hughes-Hallett, Archie; Mayer, Erik K; Marcus, Hani J; Cundy, Thomas P; Pratt, Philip J; Parston, Greg; Vale, Justin A; Darzi, Ara W

    2014-08-01

    The objectives of this study were to assess the applicability of patents and publications as metrics of surgical technology and innovation; evaluate the historical relationship between patents and publications; develop a methodology that can be used to determine the rate of innovation growth in any given health care technology. The study of health care innovation represents an emerging academic field, yet it is limited by a lack of valid scientific methods for quantitative analysis. This article explores and cross-validates 2 innovation metrics using surgical technology as an exemplar. Electronic patenting databases and the MEDLINE database were searched between 1980 and 2010 for "surgeon" OR "surgical" OR "surgery." Resulting patent codes were grouped into technology clusters. Growth curves were plotted for these technology clusters to establish the rate and characteristics of growth. The initial search retrieved 52,046 patents and 1,801,075 publications. The top performing technology cluster of the last 30 years was minimally invasive surgery. Robotic surgery, surgical staplers, and image guidance were the most emergent technology clusters. When examining the growth curves for these clusters they were found to follow an S-shaped pattern of growth, with the emergent technologies lying on the exponential phases of their respective growth curves. In addition, publication and patent counts were closely correlated in areas of technology expansion. This article demonstrates the utility of publically available patent and publication data to quantify innovations within surgical technology and proposes a novel methodology for assessing and forecasting areas of technological innovation.

  3. Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

    Science.gov (United States)

    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 (Parthritis therapy.

  4. Quantifying Periodicity in Omics Data

    Directory of Open Access Journals (Sweden)

    Cornelia eAmariei

    2014-08-01

    Full Text Available Oscillations play a significant role in biological systems, with many examples in the fast, ultradian, circadian, circalunar and yearly time domains. However, determining periodicity in such data can be problematic. There are a number of computational methods to identify the periodic components in large datasets, such as signal-to-noise based Fourier decomposition, Fisher's g-test and autocorrelation. However, the available methods assume a sinusoidal model and do not attempt to quantify the waveform shape and the presence of multiple periodicities, which provide vital clues in determining the underlying dynamics. Here, we developed a Fourier based measure that generates a de-noised waveform from multiple significant frequencies. This waveform is then correlated with the raw data from the respiratory oscillation found in yeast, to provide oscillation statistics including waveform metrics and multi-periods. The method is compared and contrasted to commonly used statistics. Moreover we show the utility of the program in the analysis of noisy datasets and other high-throughput analyses, such as metabolomics and flow cytometry, respectively.

  5. Real-Time Measurements and Modelling on Dynamic Behaviour of SonoVue Bubbles Based on Light Scattering Technology

    Institute of Scientific and Technical Information of China (English)

    TU Juan; GUAN J.F.; MATULA T.J.; Crum L.A.; WEI Rong-jue

    2008-01-01

    The dynamic behaviour of SonoVue microbubbles a new generation ultrasound contrast agent is investigated in real time with light scattering method.Highly diluted SonoVue microbubbles are injected into a diluted gel made of xanthan gum and water.The responses of individual SonoVue bubbles to driven ultrasound pulses are measured.Both linear and nonlinear bubble oscillations are observed and the results suggest that SonoVue microbubbles can generate strong nonlinear responses.By fitting the experimental data of individual bubble responses with Sarkar's model,the shell coating parameter of the bubbles and dilatational viscosity is estimated to be 7.0 nm·s·Pa.

  6. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats

    OpenAIRE

    2016-01-01

    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared wit...

  7. Permeability dependence study of the focused ultrasound-induced blood-brain barrier opening at distinct pressures and microbubble diameters using DCE-MRI

    OpenAIRE

    Vlachos, Fotios; TUNG, YAO-SHENG; Konofagou, Elisa

    2011-01-01

    Blood-brain barrier (BBB) opening using focused ultrasound (FUS) and microbubbles has been experimentally established as a non-invasive and localized brain drug delivery technique. In this study, the permeability of the opening is assessed in the murine hippocampus after the application of FUS at three different acoustic pressures and microbubble sizes. Using DCE-MRI, the transfer rates were estimated, yielding permeability maps and quantitative Ktrans values for a predefined region of intere...

  8. Noninvasive estimation of dynamic pressures in vitro and in vivo using the subharmonic response from microbubbles.

    Science.gov (United States)

    Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Liu, Ji-Bin; McDonald, Maureen E; Dickie, Kris; Leung, Corina; Forsberg, Flemming

    2011-10-01

    The purpose of this study was to develop and validate a noninvasive pressure estimation technique based on subharmonic emissions from a commercially available ultrasound contrast agent and scanner, unlike other studies that have either adopted a single-element transducer approach and/ or use of in-house contrast agents. Ambient pressures were varied in a closed-loop flow system between 0 and 120 mmHg and were recorded by a solid-state pressure catheter as the reference standard. Simultaneously, the ultrasound scanner was operated in pulse inversion mode transmitting at 2.5 MHz, and the unprocessed RF data were captured at different incident acoustic pressures (from 76 to 897 kPa). The subharmonic data for each pulse were extracted using band-pass filtering with averaging, and subsequently processed to eliminate noise. The incident acoustic pressure most sensitive to ambient pressure fluctuations was determined, and then the ambient pressure was tracked over 20 s. In vivo validation of this technique was performed in the left ventricle (LV) of 2 canines. In vitro, the subharmonic signal could track ambient pressure values with r(2) = 0.922 (p subharmonic signal tracked the LV pressures with r(2) > 0.790 (p subharmonic ultrasound-based pressure estimation technique, which can accurately track left ventricular pressures, has been established.

  9. Relationship between exercise-induced heart rate increase and the formation of microbubbles and high-intensity transient signals in mechanical heart valve implanted patients.

    Science.gov (United States)

    Sünbül, Ayşegül; Kırbaş, Ahmet; Tanrıkulu, Nursen; Sengül, Cihan; Dağdeviren, Bahadır; Işık, Omer

    2014-08-29

    The formation and collapse of vapor-filled bubbles near a mechanical heart valve is called cavitation. Microbubbles can be detected in vivo by doppler ultrasonography (USG) as HITS (high intensity transient signals) in cranial circulation. We investigated the relationship between exercise induced heart rate increase and HITS formation in cranial circulation. Thirty-nine mechanical heart valve implanted (8 aortic valve replacement (AVR) + mitral valve replacement (MVR), 9 AVR, 22 MVR) patients aged 18-80 years old were included in our study. Microbubbles were counted in the left ventricular cavity via transthoracic echocardiography at rest per cardiac cycle. Afterwards transcranial Doppler USG was performed and HITS were counted in each patient's middle cerebral artery at 5 min duration. Subsequently an exercise test according to the Bruce protocol was performed. After achieving maximal heart rate, microbubbles in the left ventricle and HITS were counted again. Microbubbles in the left ventricle and transcranial HITS increased after exercise significantly compared to resting values (15.79 ±10.91 microbubbles/beat vs. 26.51 ±18.00 microbubbles/beat, p exercise (r = 0.55, p increasing as the heart rate increased and more HITS were propelled to the cerebral circulation. As previously shown, HITS can alter cognitive functions. Therefore heart rate control is essential in mechanical heart valve patients to protect neurocognitive functions.