| 1. |
- Chen, Hongjian, et al.
(författare)
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On the Development of a Novel Contrast Pulse Sequence for Polymer-Shelled Microbubbles
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Ingår i: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - 0885-3010 .- 1525-8955.
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Tidskriftsartikel (refereegranskat)abstract
- Contrast agents are routinely used in ultrasound examinations. Nonlinear ultrasound imaging techniques have been developed over decades to enhance the contrast between the tissue and the blood pool after the injection of ultrasound contrast agents. In this study, we introduce a new contrast pulse sequence, CPS4. The CPS4 combines pulse inversion, sub-harmonic, and ultra-harmonic techniques to remove propagation distortion while capturing the unique sub-harmonic, and ultra-harmonic responses from ultrasound contrast agents. The novel CPS4 and conventional pulse inversion, sub-harmonic, and ultra-harmonic techniques were used to detect the presence of a research-grade, thick shell, polymer microbubble in a tissue-mimicking flow phantom. The contrast-to-tissue ratio (CTR) obtained from the applications of all techniques were compared. The results show that the highest CTR of approximately 16 dB was obtained using CPS4, which was superior to the individual reference techniques: pulse inversion, sub-harmonic, and ultra-harmonic techniques, at all scenarios considered in this study.
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| 2. |
- Chen, Hongjian, et al.
(författare)
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On the Development of a Novel Contrast Pulse Sequence for Polymer-Shelled Microbubbles
- 2021
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Ingår i: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-3010 .- 1525-8955. ; 68:5, s. 1569-1579
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Tidskriftsartikel (refereegranskat)abstract
- Contrast agents are routinely used in ultrasound examinations. Nonlinear ultrasound imaging techniques have been developed over decades to enhance the contrast between the tissue and the blood pool after the injection of ultrasound contrast agents (UCAs). In this study, we introduce a new contrast pulse sequence, CPS4. The CPS4 combines pulse inversion (PI), subharmonic (SH), and ultraharmonic (UH) techniques to remove propagation distortion while capturing the unique SH and UH responses from UCAs. The novel CPS4 and conventional PI, SH, and UH techniques were used to detect the presence of a research-grade, thick-shell, polymer microbubble in a tissue-mimicking flow phantom. The contrast-to-tissue ratios (CTRs) obtained from the applications of all techniques were compared. The results show that the highest CTR of approximately 16 dB was obtained using CPS4, which was superior to the individual reference techniques: PI, SH, and UH techniques, in all scenarios considered in this study.
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| 3. |
- Ghorbani, Morteza, et al.
(författare)
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Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers
- 2019
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Ingår i: Langmuir. - : American Chemical Society. - 0743-7463 .- 1520-5827. ; 35:40, s. 13090-13099
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Tidskriftsartikel (refereegranskat)abstract
- The attractive colloidal and physicochemical properties of cellulose nanofibers (CNFs) at interfaces have recently been exploited in the facile production of a number of environmentally benign materials, e.g. foams, emulsions, and capsules. Herein, these unique properties are exploited in a new type of CNF-stabilized perfluoropentane droplets produced via a straightforward and simple mixing protocol. Droplets with a comparatively narrow size distribution (ca. 1-5 μm in diameter) were fabricated, and their potential in the acoustic droplet vaporization process was evaluated. For this, the particle-stabilized droplets were assessed in three independent experimental examinations, namely temperature, acoustic, and ultrasonic standing wave tests. During the acoustic droplet vaporization (ADV) process, droplets were converted to gas-filled microbubbles, offering enhanced visualization by ultrasound. The acoustic pressure threshold of about 0.62 MPa was identified for the cellulose-stabilized droplets. A phase transition temperature of about 22 °C was observed, at which a significant fraction of larger droplets (above ca. 3 μm in diameter) were converted into bubbles, whereas a large part of the population of smaller droplets were stable up to higher temperatures (temperatures up to 45 °C tested). Moreover, under ultrasound standing wave conditions, droplets were relocated to antinodes demonstrating the behavior associated with the negative contrast particles. The combined results make the CNF-stabilized droplets interesting in cell-droplet interaction experiments and ultrasound imaging.
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| 4. |
- Loskutova, Ksenia, 1995-, et al.
(författare)
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A Study on the Acoustic Response of Pickering Perfluoropentane Droplets in Different Media
- 2021
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343.
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Tidskriftsartikel (refereegranskat)abstract
- Acoustic droplet vaporization (ADV) is the physical process of liquid-to-gas phase transition mediated by pressure variations in an ultrasound field. In this study, the acoustic response of novel particle-stabilized perfluoropentane droplets was studied in bulk and confined media. The oil/water interface was stabilized by cellulose nanofibers. First, their acoustic responses under idealized conditions were examined to assess their susceptibility to undergo ADV. Second, the droplets were studied in a more realistic setting and placed in a confined medium. Lastly, an imaging setup was developed and tested on the droplets. The acoustic response could be seen when the amplitude of the peak negative pressure (PNP) was above 200 kPa, suggesting that this is the vaporization pressure threshold for these droplets. Increasing the PNP resulted in a decrease in signal intensity over time, suggesting a more destructive behavior. The imaging setup was able to differentiate between the droplets and the surrounding tissue. Results obtained within this study suggest that these droplets have potential in terms of ultrasound-mediated diagnostics and therapy.
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| 5. |
- Loskutova, Ksenia, et al.
(författare)
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Assessment of the Mechanical Propertiesof Cellulose Nanofiber-Stabilized Droplets Using Acoustophoresis
- 2021
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Konferensbidrag (refereegranskat)abstract
- In this work, the compressibility of Pickering-stabilized perfluoropentane droplets was determined by using acoustophoresis. Polyamide beads with known density, size and compressibility were used to calculate the pressure amplitude inside the microchannel. The results show that the compressibility of CNF-stabilized droplets is significantly higher than for water, but lower than for pure PFC5. This shows promising potential for these droplets to be used in ultrasound-mediated clinical applications. It has also been shown that acoustophoresis can successfully measure the compressibility of pressure-sensitive particles for small USW pressure amplitudes. As the droplets relocate to pressure anti-nodes just as gas-filled microbubbles, it would be possible to study cell-droplet and cell-gasbubble in the same setup.
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| 6. |
- Loskutova, Ksenia, et al.
(författare)
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Biocompatibility of Cellulose Nanofiber-Coated Perfluoropentane Droplets
- 2023
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Konferensbidrag (refereegranskat)abstract
- The cellulose nanofiber(CNF)-shelled perfluoropentane (PFP) droplets were the subject of the evaluation in this work. CNF-shelled PFP droplets Mechanical and acoustic properties were studied previously and reported elsewhere [1-4], however more insights into the biological effects of these droplets are needed to translate previous in vitro tests into in vivo applications as drug carriers in ultrasound-mediated drug delivery. The aim of this work is to investigate the effect of CNF-shelled PFP droplets on cell viability of 4T1 cells, a murine breast cancer cell line. Cells were exposed to different concentrations of droplets with or without the addition of paclitaxel, i.e. a hydrophobic cancer drug.[1]. Ghorbani M, Olofsson K, Benjamins J-W, Loskutova K, Paulraj T, Wiklund M, Grishenkov D, Svagan A J, Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers, Langmuir 35(40): 13090-13099, 2019.[2]. Song X, Loskutova K, Chen H, Shen G, Grishenkov D, Deriving acoustic properties for perfluoropentane droplets with viscoelastic cellulose nanofiber shell via numerical simulations, The Journal of the Acoustical Society of America 150(3): 1750-1761, 2021.[3]. Loskutova K, Nimander D, Gouwy I, Chen H, Ghorbani M, Svagan A J, Grishenkov D, A Study on the Acoustic Response of Pickering Perfluoropentane Droplets in Different Media, ACS Omega 6(8): 5670-5678, 2019.[4]. Loskutova K, Olofsson K, Hammarström B, Wiklund M, Svagan A J, Grishenkov D, Measuring the Compressibility of Cellulose Nanofiber-Stabilized Microdroplets Using Acoustophoresis, Micromachines 12(12): 1465, 2021.
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| 7. |
- Loskutova, Ksenia, et al.
(författare)
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Cellulose Nanofiber-Coated Perfluoropentane Droplets: Fabrication and Biocompatibility Study
- 2023
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 18, s. 1835-1847
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the effect of cellulose nanofiber (CNF)-shelled perfluoropentane (PFP) droplets on the cell viability of 4T1 breast cancer cells with or without the addition of non-encapsulated paclitaxel.Methods: The CNF-shelled PFP droplets were produced by mixing a CNF suspension and PFP using a homogenizer. The volume size distribution and concentration of CNF-shelled PFP droplets were estimated from images taken with an optical microscope and analyzed using Fiji software and an in-house Matlab script. The thermal stability was qualitatively assessed by comparing the size distribution and concentration of CNF-shelled PFP droplets at room temperature (~22°) and 37°C. The cell viability of 4T1 cells was measured using a 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, a hemolysis assay was performed to assess blood compatibility of CNF-shelled PFP droplets.Results: The droplet diameter and concentration of CNF-shelled PFP droplets decreased after 48 hours at both room temperature and 37°C. In addition, the decrease in concentration was more significant at 37°C, from 3.50 ± 0.64× 10^6 droplets/mL to 1.94 ± 0.10× 10^6 droplets/mL, than at room temperature, from 3.65 ± 0.29× 10^6 droplets/mL to 2.56 ± 0.22× 10^6 droplets/mL. The 4T1 cell viability decreased with increased exposure time and concentration of paclitaxel, but it was not affected by the presence of CNF-shelled PFP droplets. No hemolysis was observed at any concentration of CNF-shelled PFP droplets.Conclusion: CNF-shelled PFP droplets have the potential to be applied as drug carriers in ultrasound-mediated therapy.
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| 8. |
- Loskutova, Ksenia, et al.
(författare)
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Measuring the Compressibility of Cellulose Nanofiber-Stabilized Microdroplets Using Acoustophoresis
- 2021
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Ingår i: Micromachines. - : MDPI. - 2072-666X. ; 12:12, s. 1465-
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Tidskriftsartikel (refereegranskat)abstract
- Droplets with a liquid perfluoropentane core and a cellulose nanofiber shell have the potential to be used as drug carriers in ultrasound-mediated drug delivery. However, it is necessary to understand their mechanical properties to develop ultrasound imaging sequences that enable in vivo imaging of the vaporization process to ensure optimized drug delivery. In this work, the compressibility of droplets stabilized with cellulose nanofibers was estimated using acoustophoresis at three different acoustic pressures. Polyamide particles of known size and material properties were used for calibration. The droplet compressibility was then used to estimate the cellulose nanofiber bulk modulus and compare it to experimentally determined values. The results showed that the acoustic contrast factor for these droplets was negative, as the droplets relocated to pressure antinodes during ultrasonic actuation. The droplet compressibility was 6.6-6.8 x10(-10) Pa-1, which is higher than for water (4.4x10(-10) Pa-1) but lower than for pure perfluoropentane (2.7x10(-9) Pa-1). The compressibility was constant across different droplet diameters, which was consistent with the idea that the shell thickness depends on the droplet size, rather than being constant.
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| 9. |
- Loskutova, Ksenia
(författare)
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Perfluorocarbon microdroplets stabilized by cellulose nanofibers : Toward ultrasound-mediated diagnostics and therapy
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound contrast agents consist of gas-filled micrometer-sized bubbles that are injectedinto the blood stream. Ultrasound contrast agents are an invaluable tool for ultrasound imaging of the cardiac muscle and highly vascularized structures such as kidneys and the liver. The ability of gas-filled microbubbles to enhance contrast in ultrasound imaging comes from their increased scattering ability due to significantly lower compressibility compared to surrounding soft tissues.The discovery of acoustic droplet vaporization, the phase-transition of liquid-filleddroplets into gas-filled microbubbles upon ultrasound exposure, has expanded the potential utility of ultrasound-mediated diagnostics and therapy to include applications such as gas embolization, histotripsy, and localized drug delivery. Multiple requirements are put onto both gas-filled microbubbles and phase-change contrast agents: they have to be non-toxic, acoustically active at clinically relevant pressure amplitudes, and their dynamic behavior has to be predictable to maximize the therapeutic or diagnostic effect while minimizing mechanical damage to surrounding healthy tissue. Novel designs of phase-change contrast agents that are able to undergo acoustic droplet vaporization could enable improved in vivo stability compared to conventional gas-filled ultrasound contrast agents.Pickering emulsions, with solid particles used as stabilizing agents instead of surfactants, have an increased stability compared to conventional emulsions. Cellulose-based Pickering emulsions in particular have previously been investigated for biomedical applications. Cellulose is a suitable material in biomedical applications as it originates from renewable sources, is biocompatible, and the surface can be easily modified. To the author’s current knowledge, cellulose-based Pickering emulsions have not previously been investigated for ultrasound-mediated applications. It is necessary to know the mechanical and acoustic properties of novel formulations and their impact on biological cells for their translation into in vivo research and future clinical use.In this thesis, the acoustic, mechanical, and biological properties of cellulose nanofiber(CNF)-shelled perfluoropentane (PFP) droplets, a type of Pickering emulsion, were investigated for ultrasound-mediated medical applications. Firstly, the current state-of-the-art and development of phase-change contrast agents, the mechanism behind acoustic droplet vaporization, and potential ultrasound-mediated medical applications were investigated. Secondly, a theoretical model that would describe and predict the acoustic response of CNF-shelled PFP droplets undergoing acoustic droplet vaporization was developed. Thirdly, the compressibility of CNF-shelled PFP droplets using an acoustophoretic setup was measured. Later, the effect of the geometry of the surrounding medium and acoustic parameters on the acoustic response of CNF-shelled PFP droplets was explored. Finally, the biocompatibility of CNF-shelled PFP droplets cells was investigated through a hemolysis assay and measurement of change in cell viability of breast cancer cells.The CNF shell has a significant impact on the predicted resonance behavior and compressibility of CNF-shelled PFP droplets, as it has significantly larger bulk and Young’s modulus than previously reported shell materials. The predicted linear resonance behavior was in the upper range of medical ultrasound (5-8 MHz), making harmonic imaging at optimal conditions difficult. However, it was demonstrated that CNF-shelled PFP droplets could be imaged using a nonlinear ultrasound imaging sequence at a frequency regularly used in clinics. Thus, CNF-shelled PFP droplets were able to undergo acoustic droplet vaporization at clinically relevant conditions. The peak negative pressure of the incident acoustic wave had a significant impact on the acoustic response of CNF-shelled PFP droplets, as higher acoustic pressure amplitudes resulted in a more disruptive behavior. Finally, CNF-shelled PFP droplets did not influence the cell viability of breast cancer cells. This was true regardless of whether or not a non-encapsulated cytotoxic drug with a known impact on cell viability was present. In summary, the results of this work showed that CNF-shelled PFP droplets are biocompatible and acoustically active at clinically relevant conditions, which shows that cellulose-based Pickering emulsions have potential in ultrasound-mediated diagnostics and therapy.
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| 10. |
- Loskutova, Ksenia, et al.
(författare)
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Review on Acoustic Droplet Vaporization in Ultrasound Diagnostics and Therapeutics
- 2019
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Forskningsöversikt (refereegranskat)abstract
- Acoustic droplet vaporization (ADV) is the physical process in which liquid undergoes phase transition to gas after exposure to a pressure amplitude above a certain threshold. In recent years, new techniques in ultrasound diagnostics and therapeutics have been developed which utilize microformulations with various physical and chemical properties. The purpose of this review is to give the reader a general idea on how ADV can be implemented for the existing biomedical applications of droplet vaporization. In this regard, the recent developments in ultrasound therapy which shed light on the ADV are considered. Modern designs of capsules and nanodroplets (NDs) are shown, and the material choices and their implications for function are discussed. The influence of the physical properties of the induced acoustic field, the surrounding medium, and thermophysical effects on the vaporization are presented. Lastly, current challenges and potential future applications towards the implementation of the therapeutic droplets are discussed.
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| 11. |
- Song, Xue, et al.
(författare)
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Deriving acoustic properties for perfluoropentane droplets with viscoelastic cellulose nanofiber shell via numerical simulations
- 2021
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; , s. 1750-1761
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoropentane droplets with cellulose nanofibers (CNF) shells have demonstrated better stability and easier surface modification as ultrasound contrast agents and drug delivery vehicles. This paper presents a theoretical model assuming a four-phase state “inverse antibubble,” with the core filled with gas perfluoropentane surrounded by liquid perfluoropentane. A continuous, incompressible, and viscoelastic stabilizing layer separates the core from the surrounding water. A parametric study is performed to predict the frequency-dependent attenuation coefficient, the speed of sound, and the resonance frequency of the droplets which have a mean diameter of 2.4760.95 lm. Results reveal that the CNF-stabilized perfluoropentane droplets can be modeled in a Rayleigh-Plesset like equation. We conclude that the shell strongly influences the acoustic behavior of the droplets and the resonance frequency largely depends on the initial gas cavity radius. More specifically, the peak attenuation coefficient and peak-to-peak speed of sound decrease with increasing shear modulus, shear viscosity, and shell thickness, while they increase with increasing gas cavity radius and concentration. The resonance frequency increases as shear modulus and shell thickness increase, while it decreases as shear viscosity and gas cavity radius increase. It is worth mentioning that droplet concentration has no effect on the resonance frequency.
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